| 1. |
- Aidas, Kestutis, et al.
(författare)
-
A quantum mechanics/molecular dynamics study of electric field gradient fluctuations in the liquid phase. The case of Na+ in aqueous solution
- 2013
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 15:5, s. 1621-1631
-
Tidskriftsartikel (refereegranskat)abstract
- The Na-23 quadrupolar coupling constant of the Na+ ion in aqueous solution has been predicted using molecular dynamics simulations and hybrid quantum mechanics/molecular mechanics methods for the calculation of electric field gradients. The developed computational approach is generally expected to provide reliable estimates of the quadrupolar coupling constants of monoatomic species in condensed phases, and we show here that intermolecular polarization and non-electrostatic interactions are of crucial importance as they result in a 100% increased quadrupolar coupling constant of the ion as compared to a simpler pure electrostatic picture. These findings question the reliability of the commonly applied classical Sternheimer approximation for the calculations of the electric field gradient. As it can be expected from symmetry considerations, the quadrupolar coupling constants of the 5- and 6-coordinated Na+ ions in solution are found to differ significantly.
|
|
| 2. |
- Aidas, Kestutis, et al.
(författare)
-
Gauge-origin independent magnetizabilities from hybrid quantum mechanics/molecular mechanics models: Theory and applications to liquid water
- 2007
-
Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614. ; 442:4-6, s. 322-328
-
Tidskriftsartikel (refereegranskat)abstract
- The theory of a hybrid quantum mechanics/molecular mechanics (QM/MM) approach for gauge-origin independent calculations of the molecular magnetizability using Hartree-Fock or Density Functional Theory is presented. The method is applied to liquid water using configurations generated from classical Molecular Dynamics simulation to calculate the statistical averaged magnetizability. Based on a comparison with experimental data, treating only one water molecule quantum mechanically appears to be insufficient, while a quantum mechanical treatment of also the first solvation shell leads to good agreement between theory and experiment. This indicates that the gas-to-liquid phase shift for the molecular magnetizability is to a large extent of non-electrostatic nature. (c) 2007 Elsevier B.V. All rights reserved.
|
|
| 3. |
- Aidas, Kestutis, et al.
(författare)
-
On the performance of quantum chemical methods to predict solvatochromic effects: The case of acrolein in aqueous solution.
- 2008
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 128:19, s. 1-194503
-
Tidskriftsartikel (refereegranskat)abstract
- The performance of the Hartree-Fock method and the three density functionals B3LYP, PBE0, and CAM-B3LYP is compared to results based on the coupled cluster singles and doubles model in predictions of the solvatochromic effects on the vertical n-->pi(*) and pi-->pi(*) electronic excitation energies of acrolein. All electronic structure methods employed the same solvent model, which is based on the combined quantum mechanics/molecular mechanics approach together with a dynamical averaging scheme. In addition to the predicted solvatochromic effects, we have also performed spectroscopic UV measurements of acrolein in vapor phase and aqueous solution. The gas-to-aqueous solution shift of the n-->pi(*) excitation energy is well reproduced by using all density functional methods considered. However, the B3LYP and PBE0 functionals completely fail to describe the pi-->pi(*) electronic transition in solution, whereas the recent CAM-B3LYP functional performs well also in this case. The pi-->pi(*) excitation energy of acrolein in water solution is found to be very dependent on intermolecular induction and nonelectrostatic interactions. The computed excitation energies of acrolein in vacuum and solution compare well to experimental data.
|
|
| 4. |
- Aidas, Kestutis, et al.
(författare)
-
Photoabsorption of Acridine Yellow and Proflavin Bound to Human Serum Albumin Studied by Means of Quantum Mechanics/Molecular Dynamics
- 2013
-
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 117:7, s. 2069-2080
-
Tidskriftsartikel (refereegranskat)abstract
- Attempting to unravel mechanisms in optical probing of proteins, we have performed pilot calculations of two cationic chromophores-acridine yellow and proflavin-located at different binding sites within human serum albumin, including the two primary drug binding sites as well as a heme binding site. The computational scheme adopted involves classical molecular dynamics simulations of the ligands bound to the protein and subsequent linear response polarizable embedding density functional theory calculations of the excitation energies. A polarizable embedding potential consisting of point charges fitted to reproduce the electrostatic potential and isotropic atomic polarizabilities computed individually for every residue of the protein was used in the linear response calculations. Comparing the calculated aqueous solution-to-protein shifts of maximum absorption energies to available experimental data, we concluded that the cationic proflavin chromophore is likely not to bind albumin at its drug binding site I nor at its heme binding site. Although agreement with experimental data could only be obtained in qualitative terms, our results clearly indicate that the difference in optical response of the two probes is due to deprotonation, and not, as earlier suggested, to different binding sites. The ramifications of this finding for design of molecular probes targeting albumin or other proteins is briefly discussed.
|
|
| 5. |
- Aidas, Kestutis, et al.
(författare)
-
Solvent effects on NMR isotropic shielding constants. A comparison between explicit polarizable discrete and continuum approaches
- 2007
-
Ingår i: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1520-5215. ; 111:20, s. 4199-4210
-
Tidskriftsartikel (refereegranskat)abstract
- The gas-to-aqueous solution shifts of the O-17 and C-13 NMR isotropic shielding constants for the carbonyl chromophore in formaldehyde and acetone are investigated. For the condensed-phase problem, we use the hybrid density functional theory/molecular mechanics approach in combination with a statistical averaging over an appropriate number of solute-solvent configurations extracted from classical molecular dynamics simulations. The PBE0 exchange-correlation functional and the 6-311++G(2d,2p) basis set are used for the calculation of the shielding constants. London atomic orbitals are employed to ensure gauge-origin independent results. The effects of the bulk solvent molecules are found to be crucial in order to calculate accurate solvation shifts of the shielding constants. Very good agreement between the computed and experimental solvation shifts is obtained for the shielding constants of acetone when a polarizable water potential is used. Supermolecular results based on geometry-optimized molecular structures are presented. We also compare the results obtained with the polarizable continuum model to the results obtained using explicit MM molecules to model the bulk solvent effect.
|
|
| 6. |
- Aidas, Kestutis, et al.
(författare)
-
The Dalton quantum chemistry program system
- 2014
-
Ingår i: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
-
Tidskriftsartikel (refereegranskat)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
|
|
| 7. |
- Eriksen, Janus J., et al.
(författare)
-
Computational Protocols for Prediction of Solute NMR Relative Chemical Shifts. A Case Study of L-Tryptophan in Aqueous Solution
- 2011
-
Ingår i: Journal of Computational Chemistry. - : Wiley. - 0192-8651 .- 1096-987X. ; 32:13, s. 2853-2864
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we have applied two different spanning protocols for obtaining the molecular conformations of L-tryptophan in aqueous solution, namely a molecular dynamics simulation and a molecular mechanics conformational search with subsequent geometry re-optimization of the stable conformers using a quantum mechanically based method. These spanning protocols represent standard ways of obtaining a set of conformations on which NMR calculations may be performed. The results stemming from the solute-solvent configurations extracted from the MD simulation at 300 K are found to be inferior to the results stemming from the conformations extracted from the MM conformational search in terms of replicating an experimental reference as well as in achieving the correct sequence of the NMR relative chemical shifts of L-tryptophan in aqueous solution. We find this to be due to missing conformations visited during the molecular dynamics run as well as inaccuracies in geometrical parameters generated from the classical molecular dynamics simulations.
|
|
| 8. |
- Frecus, Bogdan, et al.
(författare)
-
EPR spin Hamiltonian parameters of encapsulated spin-labels : impact of the hydrogen bonding topology
- 2013
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 15:7, s. 2427-2434
-
Tidskriftsartikel (refereegranskat)abstract
- Encapsulation of spin-labels into "host'' compounds, like cucurbit[n]urils or cyclodextrins, in solutions has profound effects on the EPR spin Hamiltonian parameters of the spin-labels. In this work we study the microscopic origin of the EPR spin Hamiltonian parameters of spin-labels enclosed in hydrophobic cavities. We focus on the dependence of the EPR properties of encapsulated spin-labels on the hydrogen bonding topologies that occur upon encapsulation, and quantize various contributions to these parameters according to specific hydrogen bonding patterns. The obtained results provide refined insight into the role of the hydrogen bonding induced encapsulation shifts of EPR spin Hamiltonian parameters in solvated "spin-label@host compound'' complexes.
|
|
| 9. |
- Genheden, Samuel, et al.
(författare)
-
Accurate Predictions of Nonpolar Solvation Free Energies Require Explicit Consideration of Binding-Site Hydration
- 2011
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 133:33, s. 13081-13092
-
Tidskriftsartikel (refereegranskat)abstract
- Continuum solvation methods are frequently used to increase the efficiency of computational methods to estimate free energies. In this paper, we have evaluated how well such methods estimate the nonpolar solvation free-energy change when a ligand binds to a protein. Three different continuum methods at various levels of approximation were considered, viz., the polarized continuum model (PCM), a method based on cavity and dispersion terms (CD), and a method based on a linear relation to the solvent-accessible surface area (SASA). Formally rigorous double-decoupling thermodynamic integration was used as a benchmark for the continuum methods. We have studied four protein-ligand complexes with binding sites of varying solvent exposure, namely the binding of phenol to ferritin, a biotin analogue to avidin, 2-aminobenzimidazole to trypsin, and a substituted galactoside to galectin-3. For ferritin and avidin, which have relatively hidden binding sites, rather accurate nonpolar solvation free energies could be obtained with the continuum methods if the binding site is prohibited to be filled by continuum water in the unbound state, even though the simulations and experiments show that the ligand replaces several water molecules upon binding. For the more solvent exposed binding sites of trypsin and galectin-3, no accurate continuum estimates could be obtained, even if the binding site was allowed or prohibited to be filled by continuum water. This shows that continuum methods fail to give accurate free energies on a wide range of systems with varying solvent exposure because they lack a microscopic picture of binding-site hydration as well as information about the entropy of water molecules that are in the binding site before the ligand binds. Consequently, binding affinity estimates based upon continuum solvation methods will give absolute binding energies that may differ by up to 200 kJ/mol depending on the method used. Moreover, even relative energies between ligands with the same scaffold may differ by up to 75 kJ/mol. We have tried to improve the continuum solvation methods by adding information about the solvent exposure of the binding site or the hydration of the binding site, and the results are promising at least for this small set of complexes.
|
|
| 10. |
- Genheden, Samuel, et al.
(författare)
-
Nonpolar Solvation Free Energies of Protein-Ligand Complexes
- 2010
-
Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 6:11, s. 3558-3568
-
Tidskriftsartikel (refereegranskat)abstract
- Recent investigations have indicated that different solvation methods give qualitatively different results for the nonpolar solvation contribution to ligand-binding affinities. Therefore, we have calculated the nonpolar solvation contribution to the free energy of benzene binding to the T4 lysozyme Leu99Ala mutant using thermodynamic integration (TI) and three approximate methods. The total binding free energy was calculated with TI and then decomposed into contributions from the solvent and the solute. The nonpolar contribution from the solute was compared to approximate methods within the framework of the molecular-mechanics and generalized Born with surface area method (MM/GBSA). First, the nonpolar solvation energy was calculated with a linear relation to the solvent-accessible surface area (SASA). Second, a recent approach that divides the nonpolar solvation energy into cavity and dispersion parts was used, and third, the nonpolar solvation energy was calculated with the polarized continuum model (PCM). Surprisingly, the simple SASA estimate reproduces the TI results best. However, the reason for this is that all continuum methods assume that the benzene cavity is filled with water for the free protein, contrary to both experimental and simulation results. We present a method to avoid this assumption and then, PCM provides results that are closest to the results obtained with TI.
|
|
| 11. |
- Hansen, Mikkel Bo, et al.
(författare)
-
A virtual vibrational self-consistent-field method for efficient calculation of molecular vibrational partition functions and thermal effects on molecular properties.
- 2008
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 128:17, s. 1-174106
-
Tidskriftsartikel (refereegranskat)abstract
- A new method is described for the calculation of molecular vibrational partition functions and thermal effects on molecular properties including an explicit account of anharmonicity. The approach is based on the vibrational self-consistent-field method. Partition functions and thermal averages of the energies calculated with the new method are generally in good agreement with the result of more accurate methods. At lower temperatures the method gives in addition good results for thermal averages of dipole moments and polarizabilities. The new method is much more efficient than explicit sum-over-states approaches previously used for calculation of thermal averages. Unlike the standard sum-over-states approach, the newly developed method is feasible for larger systems despite the formal exponential increase in the number of states with the size of the system. Thus, it is presently the only practical way for including an explicit treatment of anharmonicity in vibrational wave function based calculations of molecular vibrational partition functions and thermally averaged properties of larger molecules.
|
|
| 12. |
- Hansen, Mikkel, et al.
(författare)
-
Vibrational Contributions to Indirect Spin-Spin Coupling Constants Calculated via Variational Anharmonic Approaches.
- 2008
-
Ingår i: Journal of physical chemistry. A. - : American Chemical Society (ACS). - 1520-5215 .- 1089-5639. ; 112:36, s. 8436-8445
-
Tidskriftsartikel (refereegranskat)abstract
- Zero-point vibrational contributions to indirect spin-spin coupling constants for N 2, CO, HF, H 2O, C 2H 2, and CH 4 are calculated via explicitly anharmonic approaches. Thermal averages of indirect spin-spin coupling constants are calculated for the same set of molecules and for C 2X 4, X = H, F, Cl. Potential energy surfaces have been calculated on a grid of points and analytic representations have been obtained by a linear least-squares fit in a direct product polynomial basis. Property surfaces have been represented by a fourth-order Taylor expansion around the equilibrium geometry. The electronic structure calculations employ density functional theory, and vibrational contributions to indirect spin-spin coupling constants are calculated employing vibrational self-consistent-field and vibrational configuration-interaction methods. The performance of vibrational perturbation theory and various approximate variational calculations are discussed. Thermal averages are computed by state-specific and virtual vibrational self-consistent-field methods.
|
|
| 13. |
- Hede, Thomas, et al.
(författare)
-
Simulations of Light Absorption of Carbon Particles in Nanoaerosol Clusters
- 2014
-
Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 118:10, s. 1879-1886
-
Tidskriftsartikel (refereegranskat)abstract
- Black carbon soot (BS) is considered to be the second most contributing organic matter next to carbon dioxide for the global warming effect. There is, however, so far no consensus on the quantitative warming effect due to the increased distribution of black carbon in the atmosphere. A recent report (Science 2012, 337, 1078) suggests that due to BS there is only a few percentage enhancement in absorption of BS-immersed aerosols. To get proper interpretation of the available experimental data, it becomes essential to obtain details of the microscopic origin of the absorption and scattering processes of the aerosol clusters due to the presence of soot. However, so far, due to the large spatial scale and the need for a quantum mechanical description of the particles involved in the absorption and scattering, this quest has posed an insurmountable challenge. In the present work we propose the use of a multiscale integrated approach based on molecular dynamics and a quantum mechanical molecular mechanical method to model the optical property of molecules immersed in nanosized aerosol particles. We choose fluoranthene (FA) with varying cis-pinonic acid (CPA) impurity concentration as an illustrative example of application. We observe that normally FA tends to be on the surface of the nanoaerosols but in the presence of CPA impurities its spatial location changes to a core aggregate to some extent. We find that the absorption maximum is only slightly red-shifted in the presence of increased CPA concentrations and that the oscillator strengths are not altered significantly. The comparable values for the oscillator strengths of all the low energy excitations suggest that the absorption enhancement of the aerosol due to BS will not be substantial, which is in line with the recent experimental report in Science.
|
|
| 14. |
- Hedegard, Erik Donovan, et al.
(författare)
-
Multiscale Modeling of the Active Site of [Fe] Hydrogenase: The H-2 Binding Site in Open and Closed Protein Conformations
- 2015
-
Ingår i: Angewandte Chemie (International edition). - : Wiley. - 1521-3773. ; 54:21, s. 6246-6250
-
Tidskriftsartikel (refereegranskat)abstract
- A series of QM/MM optimizations of the full protein of [Fe] hydrogenase were performed. The FeGP cofactor has been optimized in the water-bound resting state (1), with a side-on bound dihydrogen (2), or as a hydride intermediate (3). For inclusion of H4MPT in the closed structure, advanced multiscale modeling appears to be necessary, especially to obtain reliable distances between CH-H4MPT+ and the dihydrogen (H-2) or hydride (H-) ligand in the FeGP cofactor. Inclusion of the full protein is further important for the relative energies of the two intermediates 2 and 3. We finally find that hydride transfer from 3 has a significantly higher barrier than found in previous studies neglecting the full protein environment.
|
|
| 15. |
- Hedegard, Erik Donovan, et al.
(författare)
-
Theoretical Fe-57 Mossbauer spectroscopy: isomer shifts of [Fe]- hydrogenase intermediates
- 2014
-
Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084. ; 16:10, s. 4853-4863
-
Tidskriftsartikel (refereegranskat)abstract
- Mossbauer spectroscopy is an indispensable spectroscopic technique and analytical tool in iron coordination chemistry. The linear correlation between the electron density at the nucleus ("contact density'') and experimental isomer shifts has been used to link calculated contact densities to experimental isomer shifts. Here we have investigated relativistic methods of systematically increasing sophistication, including the eXact 2-Component (X2C) Hamiltonian and a finite-nucleus model, for the calculation of isomer shifts of iron compounds. While being of similar accuracy as the full four-component treatment, X2C calculations are far more efficient. We find that effects of spin-orbit coupling can safely be neglected, leading to further speedup. Linear correlation plots using effective densities rather than contact densities versus experimental isomer shift lead to a correlation constant a = -0.294 a(0)(-3) mm s(-1) (PBE functional) which is close to an experimentally derived value. Isomer shifts of similar quality can thus be obtained both with and without fitting, which is not the case if one pursues a priori a non-relativistic model approach. As an application for a biologically relevant system, we have studied three recently proposed [ Fe]-hydrogenase intermediates. The structures of these intermediates were extracted from QM/MM calculations using large QM regions surrounded by the full enzyme and a solvation shell of water molecules. We show that a comparison between calculated and experimentally observed isomer shifts can be used to discriminate between different intermediates, whereas calculated atomic charges do not necessarily correlate with Mossbauer isomer shifts. Detailed analysis reveals that the difference in isomer shifts between two intermediates is due to an overlap effect.
|
|
| 16. |
- Hedegård, Erik Donovan, et al.
(författare)
-
Relativistic Polarizable Embedding
- 2017
-
Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 13:6, s. 2870-2880
-
Tidskriftsartikel (refereegranskat)abstract
- Most chemistry, including chemistry where relativistic effects are important, occurs in an environment, and in many cases, this environment has a significant effect on the chemistry. In nonrelativistic quantum chemistry, a lot of progress has been achieved with respect to including environments such as a solvent or protein in the calculations, and now is the time to extend the possibilities for also doing this in relativistic quantum chemistry. The polarizable embedding (PE) model efficiently incorporates electrostatic effects of the environment by describing it as a collection of localized electric multipoles and polarizabilities obtained through quantum chemical calculations. In this article, we present the theory and implementation of four-and exact two-component Hamiltonians within a PE framework. We denote the methods the PE-4c-DFT and PE-X2C-DFT models. The models include a linear response formalism to calculate time-dependent (TD) properties: PE-TD-4c-DFT and PE-TD-X2C-DFT. With this first implementation, we calculate the PE-TD-4c-PBE0 excitation energies of the TcO4 - and ReO4 - ions in an explicit water solvent. This initial investigation focuses on the relative size of relativistic and solvent contributions to the excitation energies. The solvent effect is divided into an indirect solvent effect due to the structural perturbation of the XO4 - ion and a direct electrostatic effect. The relativistic effects as well as both types of solvent effects are found to contribute to a shift in the excitation energies, but they do so to different extents depending on the ion and the electronic transition in question.
|
|
| 17. |
- Jiang, Xiangyi, et al.
(författare)
-
Molecular design opportunities presented by solvent-exposed regions of target proteins
- 2019
-
Ingår i: Medicinal research reviews (Print). - : John Wiley & Sons. - 0198-6325 .- 1098-1128. ; 39:6, s. 2194-2238
-
Forskningsöversikt (refereegranskat)abstract
- Solvent-exposed regions, or solvent-filled pockets, within or adjacent to the ligand-binding sites of drug-target proteins provide opportunities for substantial modifications of existing small-molecular drug molecules without serious loss of activity. In this review, we present recent selected examples of exploitation of solvent-exposed regions of proteins in drug design and development from the recent medicinal-chemistry literature.
|
|
| 18. |
|
|
| 19. |
- Kongsted, Jacob, et al.
(författare)
-
An improved method to predict the entropy term with the MM/PBSA approach.
- 2009
-
Ingår i: Journal of Computer-Aided Molecular Design. - : Springer Science and Business Media LLC. - 1573-4951 .- 0920-654X. ; 23, s. 63-71
-
Tidskriftsartikel (refereegranskat)abstract
- A method is suggested to calculate improved entropies within the MM/PBSA approach (molecular mechanics combined with Poisson-Boltzmann and surface area calculations) to estimate protein-ligand binding affinities. In the conventional approach, the protein is truncated outside ~8 A from the ligand. This system is freely minimised using a distance-dependent dielectric constant (to simulate the removed protein and solvent). However, this can lead to extensive changes in the molecular geometry, giving rise to a large standard deviation in this term. In our new approach, we introduce a buffer region ~4 A outside the truncated protein (including solvent molecules) and keep it fixed during the minimisation. Thereby, we reduce the standard deviation by a factor of 2-4, ensuring that the entropy term no longer limits the precision of the MM/PBSA predictions. The new method is tested for the binding of seven biotin analogues to avidin, eight amidinobenzyl-indole-carboxamide inhibitors to factor Xa, and two substrates to cytochrome P450 3A4 and 2C9. It is shown that it gives more stable results and often improved predictions of the relative binding affinities.
|
|
| 20. |
- Kongsted, Jacob, et al.
(författare)
-
Coupled cluster calculations of the optical rotation of S-propylene oxide in gas phase and solution
- 2005
-
Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614. ; 401:4-6, s. 385-392
-
Tidskriftsartikel (refereegranskat)abstract
- We present ab initio calculations of the optical rotation of S-propylene oxide in both gas phase and solution using the coupled cluster methodology combined with a dielectric continuum description of the solvent. The coupled cluster calculations are performed using the CCS, CC2, CCSD and CC3 methods. None of the presented gas phase results are in accord with the experimental sign of the optical rotation at 355 nm. Thereby, the experimental sign change between the gas phase and the cyclohexane,solution optical rotation at 355 nm is not reproduced theoretically. The vibrational effects are considered to be significant and may be of crucial importance in order to bring accordance between the calculated and the experimentally established sign of the gas phase optical rotation at 355 nm. (C) 2004 Elsevier B.V. All rights reserved.
|
|
| 21. |
- Kongsted, Jacob, et al.
(författare)
-
How accurate are continuum solvation models for drug-like molecules?
- 2009
-
Ingår i: Journal of Computer-Aided Molecular Design. - : Springer Science and Business Media LLC. - 1573-4951 .- 0920-654X. ; 23:7, s. 395-409
-
Tidskriftsartikel (refereegranskat)abstract
- We have estimated the hydration free energy for 20 neutral drug-like molecules, as well as for three series of 6-11 inhibitors to avidin, factor Xa, and galectin-3 with four different continuum solvent approaches (the polarised continuum method the Langevin dipole method, the finite-difference solution of the Poisson equation, and the generalised Born method), and several variants of each, giving in total 24 different methods. All four types of methods have been thoroughly calibrated for a number of experimentally known small organic molecules with a mean absolute deviation (MAD) of 1-6 kJ/mol for neutral molecules and 4-30 kJ/mol for ions. However, for the drug-like molecules, the accuracy seems to be appreciably worse. The reason for this is that drug-like molecules are more polar than small organic molecules and that the uncertainty of the methods is proportional to the size of the solvation energy. Therefore, the accuracy of continuum solvation methods should be discussed in relative, rather than absolute, terms. In fact, the mean unsigned relative deviations of the best solvation methods, 0.09 for neutral and 0.05 for ionic molecules, correspond to 2-20 kJ/mol absolute error for the drug-like molecules in this investigation, or 2-3,000 in terms of binding constants. Fortunately, the accuracy of all methods can be improved if only relative energies within a series of inhibitors are considered, especially if all of them have the same net charge. Then, all except two methods give MADs of 2-5 kJ/mol (corresponding to an uncertainty of a factor of 2-7 in the binding constant). Interestingly, the generalised Born methods typically give better results than the Poison-Boltzmann methods.
|
|
| 22. |
- Kongsted, Jacob, et al.
(författare)
-
How to model solvent effects on molecular properties using quantum chemistry? Insights from polarizable discrete or continuum solvation models
- 2007
-
Ingår i: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1520-5215. ; 111:39, s. 9890-9900
-
Tidskriftsartikel (refereegranskat)abstract
- We present a comparative study of solvent effects on the N-15 NMR shielding constants and the lowest electronic excitation energy (n -> pi*) in the three diazines (pyrazine, pyrimidine, and pyridazine) in aqueous solution. This solvent is modeled using either a polarizable continuum model (PCM) or a discrete polarizable model (DPM). We analyze the results obtained with the two models in terms of differences/similarities in the reaction field produced at the solute. The PCM reaction field is found to be quite sensitive to the dimension of the cavity and so are the molecular properties. However, constructing the cavity so that the DPM and PCM reaction fields become similar in magnitude leads to quite similar results for the studied molecular properties modeling the solvent using either the PCM or the DPM. Compared to experimental data, the most accurate predicted results are obtained by describing the closest water molecules at the same level of sophistication as that of the solute, whereas the bulk solvent may be described using either PCM or MM. Finally, a comparison with geometry-optimized clusters seems to show that it is important to check potential deficiencies in the force field in order for this to treat hydrogen bonding in a consistent manner.
|
|
| 23. |
- Kongsted, Jacob, et al.
(författare)
-
On the accuracy of density functional theory to predict shifts in nuclear magnetic resonance shielding constants due to hydrogen bonding
- 2008
-
Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 4:2, s. 267-277
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first systematic investigation of shifts in the nuclear magnetic resonance (NMR) shielding constant due to hydrogen bonding using either the series of wave function based methods, Hartree-Fock (HF), second-order Moller-Plesset perturbation theory (MP2), Coupled Cluster Singles and Doubles (CCSD) and CCSD extended with an approximate description of triples (CCSD(T)), or Density Functional Theory (DFT) employing either the B3LYP, PBE0, or KT3 exchange correlation (xc) functionals. The molecular systems considered are (i) the water dimer and (ii) formaldehyde in complex with two water molecules. Specially for the 170 in formaldehyde we observe significant differences between the DFT and CCSD(T) predictions. However, the extent of these deviations depends crucially on the applied xc functional. Compared to CCSD(T) we find the KT3 functional to provide accurate results, whereas both B3LYP and PBE0 are in significant error. Potential consequences of this observation are discussed in the context of general predictions of NMR shielding constants in condensed phase.
|
|
| 24. |
- Kongsted, Jacob, et al.
(författare)
-
Prediction and rationalization of the pH dependence of the activity and stability of family 11 xylanases
- 2007
-
Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 46:47, s. 13581-13592
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents a study of the pH dependence of the activity and stability of a set of family 11 xylanases for which X-ray structures are available, using the PROPKA approach. The xylanases are traditionally divided into basic and acidic xylanases, depending on whether the catalytic acid is hydrogen bonded to an Asn or Asp residue. Using X-ray structures, the predicted pH values of optimal activity of the basic xylanases are in the range of 5.2-6.9, which is in reasonable agreement with the available experimental values of 5-6.5. In the case of acidic xylanases, there are only four X-ray structures available, and using these structures, the predicted pHs of optimal activity are in the range of 4.2-5.0, compared to an observed range of 2-4.6. The influence of dynamical fluctuations of the protein structure is investigated for Bacillus agaradhaerens and Aspergillus kawachii xylanase using molecular dynamics (MD) simulations to provide snapshots from which average values can be computed. This decreases the respective predicted pH optima from 6.2-6.7 and 4.8 to 5.3 +/- 0.3 and 4.0 +/- 0.2, respectively, which are in better agreement with the observed values of 5.6 and 2, respectively. The change is primarily due to structural fluctuations of an Arg residue near the catalytic nucleophile, which lowers its pK(a) value compared to using the X-ray structure. The MD simulations and some X-ray structures indicate that this Arg residue can form a hydrogen bond to the catalytic base, and it is hypothesized that this hydrogen bond is stabilized by an additional hydrogen bond to another Glu residue present only in acidic xylanases. Formation of such a hydrogen bond is predicted to lower the pH optimum of A. kawachii xylanase to 2.9 +/- 0.3, which is in reasonable agreement, with the observed value of 2. The predicted pH of optimal stability is in excellent agreement with the pH value at which the melting temperature (T-m) is greatest. Some correlation is observed between the pH-dependent free energy of unfolding and T-m, suggesting that the thermostability of the xylanases is partly due to a difference in residues with shifted pK(a) values. Thus, the thermostability of xylanases (and proteins in general) can perhaps be increased by mutations that introduce ionizable residues with pK(a) values significantly lower than standard values.
|
|
| 25. |
- Kongsted, Jacob, et al.
(författare)
-
Solvent effects on zero-point vibrational corrections to optical rotations and nuclear magnetic resonance shielding constants
- 2008
-
Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614. ; 451:4-6, s. 226-232
-
Tidskriftsartikel (refereegranskat)abstract
- We present a study of solvent effects on the zero-point vibrational corrections (ZPVC) to optical rotations and nuclear magnetic resonance shielding constants of solvated molecules. The model used to calculate vibrational corrections rely on an expansion of the potential and property surfaces around an effective molecular geometry and includes both harmonic and anharmonic correction. Numerical examples are presented for (S)-propylene oxide in various solvents as well as for acetone and the three diazene molecule. We find that solvent effects on the ZPVCs may be significant and in some cases crucial to accurately predict solvent shifts on molecular properties.
|
|
| 26. |
- Kongsted, Jacob, et al.
(författare)
-
The QM/MM approach for wavefunctions, energies and response functions within self-consistent field and coupled cluster theories
- 2002
-
Ingår i: Molecular Physics. - : Informa UK Limited. - 1362-3028 .- 0026-8976. ; 100:11, s. 1813-1828
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents the coupled cluster/molecular mechanics (CC/MM) and self-consistent field/molecular mechanics (SCF/MM) approaches for wavefunctions, energies and response properties. Two physically different theories are derived, the mean-field and the direct-field interaction approaches, together with expressions for the optimization condition of both variational and non-variational wavefunctions and energies. Also derived are the linear response functions at the CC/MM and SCF/MM levels of theory, and the expressions are compared with the vacuum response functions.
|
|
| 27. |
- Kongsted, Jacob, et al.
(författare)
-
Vibrational and thermal effects on the dipole polarizability of methane and carbon tetrachloride from vibrational structure calculations
- 2007
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 127:15
-
Tidskriftsartikel (refereegranskat)abstract
- We present a theoretical study of vibrational and thermal effects on the dipole polarizability of methane and carbon tetrachloride. Using a fourth order Taylor expansion in rectilinear normal coordinates of the potential and property surfaces we solve the vibrational problem using vibrational structure theory, e.g., through vibrational self-consistent-field or vibrational configuration-interaction theory. For each vibrational state we calculate in addition the vibrational state average polarizability. Constructing the vibrational partition function by "brute force" allows for prediction of thermal effects on the dipole polarizability. The method is not restricted in any way to polarizabilities nor to the specific representation of the potential and property surfaces employed in this work. Any molecular property with a suitable normal coordinate representation may be considered. We discuss the performance of vibrational self-consistent field as compared to vibrational configuration interaction and study in detail the convergence of the former method with respect to the number of vibrational states included in the thermal averaging. Based on calculations including up to 170 000 vibrational self-consistent-field states we present thermal effects on the dipole polarizability of methane and carbon tetrachloride in the temperature ranges 0-1100 and 0-500 K, respectively. The predicted thermal effect on the dipole polarizability of methane is found to be similar to 0.8% which compare well with previous experimental measurements. (C) 2007 American Institute of Physics.
|
|
| 28. |
- Li, Xin, et al.
(författare)
-
Binding Mechanism and Magnetic Properties of a Multifunctional Spin Label for Targeted EPR Imaging of Amyloid Proteins : Insight from Atomistic Simulations and First-Principles Calculations
- 2012
-
Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 8:11, s. 4766-4774
-
Tidskriftsartikel (refereegranskat)abstract
- Electron paramagnetic resonance (EPR) imaging techniques provide a promising approach to detect amyloid structures which are of paramount importance in early-stage diagnosis of conformational diseases. Here, we report a combined molecular dynamics and density functional theory/molecular mechanics computational scheme for evaluation of the binding mechanism between a multifunctional spin label and the target amyloid protein. In addition, we consider evaluation of EPR spin Hamiltonian parameters with the aim of providing a better microscopic understanding and interpretation of EPR spectroscopy. The results from molecular dynamics simulations suggest that the oligothiophene conjugate part of the spin label interacts with hydrophobic residues of the amyloid protein through hydrophobic attraction and that both the N-O bond length and the N-O out-of-plane tilt angle in the nitroxide group are slightly diminished after, complexation with the protein. The translational and rotational motions of the protein bound spin label are considerably slowed compared to those of the free spin label in aqueous solution, but interestingly, hydrogen bonds formed between the nitroxide oxygen group and the surrounding water molecules are hardly affected by the presence Of the amyloid protein. First principles calculation's suggest that EPR spin Hamiltonian parameters including the nitroxide nitrogen hyperfine coupling tensor A(N) and electronic g tensor suffer noticeable changes upon complexation with the protein. The magnitude of the A(N) tensor is found,to:be. closely related to the nitroxide N-O out tilt angle, while the g tensor is affected by both the nitroxide N-O bond length as well as the interaction between the spin label and the amyloid protein With this work we show that state-of-the-art simulation techniques represent a promising way of providing a detailed understanding of the microscopic mechanisms responsible for the formation and stability of a spin label complexed with amyloid structures as well as the magnetic properties of the free and protein-bound spin label.
|
|
| 29. |
- List, Nanna Holmgaard, et al.
(författare)
-
Excited states in large molecular systems through polarizable embedding
- 2016
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Elsevier. - 1463-9076 .- 1463-9084. ; 18:30, s. 20234-20250
-
Tidskriftsartikel (refereegranskat)abstract
- In this perspective, we provide an overview of recent work within the polarizable embedding scheme to describe properties of molecules in realistic environments of increasing complexity. After an outline of the theoretical basis for the polarizable embedding model, we discuss the importance of using an accurate embedding potential, and how this may be used to significantly reduce the size of the part of the system treated using quantum mechanics without compromising the accuracy of the final results. Furthermore, we discuss the calculation of local electronic excited states based on response theory. We finally discuss aspects related to two recent extensions of the model (i) effective external field and (ii) polarizable density embedding emphasizing their importance for efficient yet accurate description of excited-state properties in complex environments.
|
|
| 30. |
- List, Nanna Holmgaard, et al.
(författare)
-
Relation between Nonlinear Optical Properties of Push-Pull Molecules and Metric of Charge Transfer Excitations
- 2015
-
Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 11:9, s. 4182-4188
-
Tidskriftsartikel (refereegranskat)abstract
- We establish the relationships between the metric of charge transfer excitation (Delta r) for the bright pi pi* state and the two-photon absorption probability as well as the first hyperpolarizability for two families of push pull pi-conjugated systems. As previously demonstrated by Guido et al. (J. Chem. Theory Comput. 2013, 9, 3118-3126), Delta r is a measure for the average hole electron distance upon excitation and can be used to discriminate between short- and long-range electronic excitations. We indicate two new benefits from using this metric for the analyses of nonlinear optical properties of push pull systems. First, the two-photon absorption probability and the first hyperpolarizability are found to be interrelated through Delta r; if, beta similar to (Delta r)(k), then roughly, delta(TPA) similar to (Delta r)(k+1). Second, a simple power relation between Delta r and the molecular hyperpolarizabilities of push pull systems offers the possibility of estimating properties for longer molecular chains without performing calculations of high-order response functions explicitly. We further demonstrate how to link the hyperpolarizabilities with the chain length of the push-pull pi-conjugated systems through the metric of charge transfer.
|
|
| 31. |
- List, Nanna Holmgaard, 1985-
(författare)
-
Theoretical Description of Electronic Transitions in Large Molecular Systems in the Optical and X-Ray Regions
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The size and conformational complexity of proteins and other large systems represent major challenges for today's methods of quantum chemistry.This thesis is centered around the development of new computational tools to gain molecular-level insight into electronic transitions in such systems. To meet this challenge, we focus on the polarizable embedding (PE) model, which takes advantage of the fact that many electronic transitions are localized to a smaller part of the entire system.This motivates a partitioning of the large system into two regions that are treated at different levels of theory:The smaller part directly involved in the electronic process is described using accurate quantum-chemical methods, while the effects of the rest of the system, the environment, are incorporated into the Hamiltonian of the quantum region in an effective manner.This thesis presents extensions of the PE model with theaim of expanding its range of applicability to describe electronic transitions in large molecular systemsin the optical and X-ray regions. The developments cover both improvements with regardto the quantum region as well as the embedding potential representing the environment.Regarding the former, a damped linear response formulation has been implemented to allow for calculations of absorption spectra of large molecular systems acrossthe entire frequency range. A special feature of this development is its abilityto address core excitations that are otherwise not easily accessible.Another important development presented in this thesis is the coupling of the PE model to a multi-configuration self-consistent-field description of the quantum region and its further combination with response theory. In essence, this extends the PE model to the study of electronic transitions in large systems that are prone to static correlation --- a situation that is frequently encountered in biological systems. In addition to the direct environmental effects on the electronic structure of the quantum region, another important component of the description of electronic transitions in large molecular systems is an accurate account of the indirect effects of the environment, i.e., the geometrical distortions in the quantum region imposed by the environment. In thisthesis we have taken the first step toward the inclusion of geometry distortions in the PE frameworkby formulating and implementing molecular gradients for the quantum region.To identify critical points related to the environment description, we perform a theoretical analysis of the PE model starting from a full quantum-mechanicaltreatment of a composite system. Based on this, we present strategies for an accurate yet efficient construction of the embedding potentialcovering both the calculation of ground state and transition properties. The accurate representation of the environment makes it possible to reduce the size of the quantum region without compromising the overall accuracy of the final results. This further enables use of highly accurate quantum-chemical methods despite their unfavorable scaling with the size of the system.Finally, some examples of applications will be presented to demonstrate how the PE model may be applied as a tool to gain insight into and rationalize the factors influencing electronic transitions in large molecular systems of increasing complexity.
|
|
| 32. |
- Matczyszyn, Katarzyna, et al.
(författare)
-
One- and Two-Photon Absorption of a Spiropyran-Merocyanine System : Experimental and Theoretical Studies
- 2015
-
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 119:4, s. 1515-1522
-
Tidskriftsartikel (refereegranskat)abstract
- We report on the nonlinear optical properties measurements and quantum-chemical calculations of a well-known photochromic system consisting of spiropyran and the merocyanine photoproduct. The study of nonlinear absorption and refraction properties of the molecules dissolved in chloroform were performed with the Z-scan technique, using femtosecond pulses in a wide range of wavelengths. Maxima in the two-photon absorption spectrum at 700 and 1050 nm were found for the merocyanine form, and the corresponding two-photon absorption cross section is 80 GM and 20 GM, respectively. The latter feature does not vanish completely in the nonlinear spectrum of the spiropyran form, possibly because of the existence of some photoconversion caused by the laser beam during the measurements. A nonlinear absorption peak at 900 nm is found in the spiropyran form with an effective cross section of about 20 GM; it is likely due to three-photon absorption or to absorption by some intermediate species. The experimental data are supported by calculations performed with the use of a hybrid quantum mechanics-molecular mechanics approach.
|
|
| 33. |
- Mogelhoj, Andreas, et al.
(författare)
-
Solvent effects on the nitrogen NMR shielding and nuclear quadrupole coupling constants in 1-methyltriazoles
- 2008
-
Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614. ; 460:1-3, s. 129-136
-
Tidskriftsartikel (refereegranskat)abstract
- In this Letter, we use a discrete polarizable solvation model for a systematic analysis of the solvent effects on the nitrogen NMR shielding and nuclear quadrupole coupling constants in a series of 1-methyltriazoles. Fairly accurate predictions are found for the solvent shifts of the nitrogen NMR shielding constants. The analysis of the relative half-height widths of the resonance signal predicted in either vacuum or aqueous solution implies that the spin relaxation time for the pyridine- and pyrrole-type nitrogen atoms possess similar magnitudes in vacuum whereas they are different in aqueous solution. (C) 2008 Elsevier B.V. All rights reserved.
|
|
| 34. |
- Mudedla, S. K., et al.
(författare)
-
Enhancement of Internal Motions of Lysozyme through Interaction with Gold Nanoclusters and its Optical Imaging
- 2015
-
Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 119:1, s. 653-664
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the interaction of gold nanoclusters with proteins has important ramifications in various fields. We present a study of the interaction between gold nanoclusters and lysozyme investigated using classical molecular dynamics and center-of-mass pulling simulations. The results reveal that the gold nanoclusters induce significant structural changes in lysozyme. Because the internal motions of lysozyme are related to its function, the changes in these internal motions have been quantified using principal component analysis of the molecular dynamics trajectories. The internal motions of lysozyme that are important for its function have been altered because of the interaction with the gold nanocluster. We have also explored how these induced changes in the lysozyme structure affect specific optical properties of the gold nanocluster using the complex polarization propagator method within the time-dependent density functional theory framework, which is of relevance for studies of the optical imaging of lysozyme using gold nanoclusters as molecular probes.
|
|
| 35. |
- Murugan, Natarajan Arul, et al.
(författare)
-
Chelation-Induced Quenching of Two-Photon Absorption of Azacrown Ether Substituted Distyryl Benzene for Metal Ion Sensing
- 2014
-
Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 10:2, s. 778-788
-
Tidskriftsartikel (refereegranskat)abstract
- Imaging of metal ion concentration, distribution, and dynamics can pave the way to diagnose a number of diseases and to identify the normal functioning of the human body. Recently, two-photon microscopy-based imaging of metal ions has become popular due to several favorable factors as compared to fluorescence-based imaging. However, much has to be investigated in order to design probes with large two-photon absorption cross sections and yet with selective binding affinity toward metal ions. In particular, it is crucial to recognize the mechanisms of metal ion-induced changes of the two-photon absorption intensity. The present paper contributes to this effort and reports on the results of extensive studies carried out to define a reliable computational protocol that can account for sampling, solvent, and finite temperature,effects for one- and two-photon properties of metal probes, using azacrown ether substituted distyrylbenzene embedded in solvents as a testbed. We employ a selection of theoretical approaches to model the structure of the probe alone and in the presence of Mg2+ ion in acetonitrile solvent, including static quantum-chemical calculations, rigid- and flexible-body molecular dynamics, and hybrid QM/MM molecular dynamics. For a set of solute-solvent configurations, the one- and the two-photon properties are computed using the recently developed polarizable embedding response approach. It is found that the hybrid QM/MM molecular dynamics based approach is the most successful one among other employed computational strategies, viz, reproduction of the metal ion-induced blue shift in the absorption wavelength and decrease in the two-photon absorption cross section, which actually is in excellent agreement with experimental data. The mechanism for such metal ion-induced changes in the optical properties is put forward using a few-state model. Possible design principles to tune the two-photon absorption properties of probes are also discussed.
|
|
| 36. |
- Murugan, Natarajan Arul, et al.
(författare)
-
pH-Induced Modulation of One- and Two-Photon Absorption Properties in a Naphthalene-Based Molecular Probe
- 2013
-
Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 9:8, s. 3660-3669
-
Tidskriftsartikel (refereegranskat)abstract
- Presently, there is a great demand for small probe molecules that can be used for two-photon excitation microscopy (TPM)-based monitoring of intracellular and intraorganelle activity and pH. The candidate molecules should ideally possess a large two-photon absorption cross section with optical properties sensitive to pH changes. In the present work, we investigate the potential of a methoxy napthalene (MONAP) derivative for its suitability to serve as a pH sensor using TPM. Using an integrated approach rooted in hybrid quantum mechanics/molecular mechanics, the structures, dynamics, and the one- and two-photon properties of the probe in dimethylformamide solvent are studied. It is found that the protonated form is responsible for the optical property of MONAP at moderately low pH, for which the calculated pH-induced red shift is in good agreement with experiments. A 2-fold increase in the two-photon absorption cross section in the IR region of the spectrum is predicted for the moderately low pH form of the probe, suggesting that this can be a potential probe for pH monitoring of living cells. We also propose some design principles aimed at obtaining control of the absorption spectral range of the probe by structural tuning. Our work indicates that the integrated approach employed is capable of capturing the pH-induced changes in structure and optical properties of organic molecular probes and that such in silico tools can be used to draw structure-property relationships to design novel molecular probes suitable for a specific application.
|
|
| 37. |
- Murugan, N. Arul, et al.
(författare)
-
Promising two-photon probes for in vivo detection of beta amyloid deposits
- 2014
-
Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 50:79, s. 11694-11697
-
Tidskriftsartikel (refereegranskat)abstract
- Based on electronic structure calculations we propose that particular small-sized organic molecules - donor-acceptor substituted phenyl polymethines - can be used as two-photon diagnostic probes for non-invasive imaging of amyloid oligomers and fibrils, which are often referred to as the "early signatures'' of Alzheimer's disease.
|
|
| 38. |
- Nabo, Lina J., et al.
(författare)
-
Embedding beyond electrostatics-The role of wave function confinement
- 2016
-
Ingår i: Journal of Chemical Physics. - : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 145:10
-
Tidskriftsartikel (refereegranskat)abstract
- We study excited states of cholesterol in solution and show that, in this specific case, solute wave-function confinement is the main effect of the solvent. This is rationalized on the basis of the polarizable density embedding scheme, which in addition to polarizable embedding includes non-electrostatic repulsion that effectively confines the solute wave function to its cavity. We illustrate how the inclusion of non-electrostatic repulsion results in a successful identification of the intense pi ->pi* transition, which was not possible using an embedding method that only includes electrostatics. This underlines the importance of non-electrostatic repulsion in quantum-mechanical embedding-based methods.
|
|
| 39. |
- Natarajan Arul, Murugan, et al.
(författare)
-
Amyloid Fibril-Induced Structural and Spectral Modifications in the Thioflavin-T Optical Probe
- 2013
-
Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 4:1, s. 70-77
-
Tidskriftsartikel (refereegranskat)abstract
- Motivated by future possibilities to design target molecules for fibrils with diagnostic or therapeutic capability related to amyloidosis diseases, we investigate in this work the dielectric nature of amyloid fibril microenvironments in different binding sites using an optical probe, thioflavin-T (THT), which has been used extensively to stain such fibrils. We study the fibril-environment-induced structural and spectral changes of THT at each binding site and compare the results to the fibril-free situation in aqueous solution. All binding sites are found to show a similar effect with respect to the conformational changes of THT; in the presence of the fibril, its molecular geometry tends to become planarized. However, depending on the dielectric nature of the specific binding site, a red shift, blue shift, or no shift in the absorption spectra of THT is predicted. Interestingly, the experimentally measured red shift in the spectra is seen only when THT binds to one of the core or surface-binding sites. It is found that the dielectric nature of the microenvironment in the fibril is strongly nonhomogeneous.
|
|
| 40. |
- Natarajan Arul, Murugan, et al.
(författare)
-
Association dynamics and linear and nonlinear optical properties of an N-acetylaladanamide probe in a POPC membrane
- 2013
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 135:36, s. 13590-13597
-
Tidskriftsartikel (refereegranskat)abstract
- Along with the growing evidence that relates membrane abnormalities to various diseases, biological membranes have been acknowledged as targets for therapy. Any such abnormality in the membrane structure alters the membrane potential which in principle can be captured by measuring properties of specific optical probes. There exists by now many molecular probes with absorption and fluorescence properties that are sensitive to local membrane structure and to the membrane potential. To suggest new high-performance optical probes for membrane-potential imaging it is important to understand in detail the membrane-induced structural changes in the probe, the membrane association dynamics of the probe, and its membrane-specific optical properties. To contribute to this effort, we here study an optical probe, N-acetylaladanamide (NAAA), in the presence of a POPC lipid bilayer using a multiscale integrated approach to assess the probe structure, dynamics, and optical properties in its membrane-bound status and in water solvent. We find that the probe eventually assimilates into the membrane with a specific orientation where the hydrophobic part of the probe is buried inside the lipid bilayer, while the hydrophilic part is exposed to the water solvent. The computed absorption maximum is red-shifted when compared to the gas phase. The computations of the two-photon absorption and second harmonic generation cross sections of the NAAA probe in its membrane-bound state which is of its first kind in the literature suggest that this probe can be used for imaging the membrane potential using nonlinear optical microscopy.
|
|
| 41. |
- Natarajan Arul, Murugan, et al.
(författare)
-
Breakdown of the first hyperpolarizability/bond-length alternation parameter relationship
- 2010
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:38, s. 16453-16458
-
Tidskriftsartikel (refereegranskat)abstract
- We have investigated the dependence of the static first hyperpolarizability on the bond-length alternation (BLA) parameter. Our analysis indicates that the validity of the first hyperpolarizability/BLA parameter relationship is restricted to the no-field, vacuum, limit, while it successively breaks down along with increasing polarity of a surrounding medium, becoming invalid, for instance, in an aqueous solution. This contention is based on a series of TD-DFT, TD-DFT/PCM and hybrid TD-DFT/MM calculations of the first hyperpolarizability for a set of molecular configurations generated from Car-Parrinello hybrid QM/MM simulations of the stilbazolium merocyanine chromophore in chloroform and water solvents, and on a rationalization by means of the two-state model for the first hyperpolarizability. The BLA dependence of the three parameters entering the two-state model is shown to be qualitatively different in vacuum and in solvents. Particularly, in the vacuum case, the difference between ground and excited state dipole moments goes to zero for a vanishing BLA, which is not true in the presence of an aqueous medium. In the aqueous medium, an opposing behavior of the parameters involved in the two-state model results in an almost constant first hyperpolarizability with varying BLA parameter.
|
|
| 42. |
- Natarajan Arul, Murugan, et al.
(författare)
-
Color modeling of protein optical probes
- 2012
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 14:3, s. 1107-1112
-
Tidskriftsartikel (refereegranskat)abstract
- We present a strategy for modeling optical probes within heterogeneous environments of restricted dimension. The method is based on a multiphysics approach comprising sequential structure modeling by means of hybrid Car-Parrinello molecular dynamics and property modeling by means of quantum mechanics/molecular mechanics response theory. For demonstration we address the structural and optical properties of nile red within the beta-lacto globulin protein. We consider the cases with the probe situated on the surface or within the cavity of the protein, or embedded in a water solvent. We find the absorption properties of the probe to be highly dependent on its position relative to the protein. Structural rearrangements of the optical probe are found to contribute significantly to these environmental effects.
|
|
| 43. |
- Natarajan Arul, Murugan, et al.
(författare)
-
Demystifying the solvatochromic reversal in Brooker's merocyanine dye
- 2011
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 13:4, s. 1290-1292
-
Tidskriftsartikel (refereegranskat)abstract
- Based on hybrid QM/MM simulation techniques, we rationalize the spectacular solvatochromic reversal behavior observed for a stilbazolium merocyanine (SM) called Brooker's merocyanine dye. This solvatochromic reversal is attributed to a change in the solute p-electron distribution from zwitterionic to neutral following the change in solvents from polar to non polar. Based on our calculations, we suggest that a polar solvent, like water, with larger relative permittivity is influential enough to bring the change in molecular structure from neutral to zwitterionic. Our results clearly indicate that SM exists in a neutral molecular structure in non polar solvents like trichloromethane and thereby we suggest that self-aggregation of SM may not occur in this solvent.
|
|
| 44. |
- Natarajan Arul, Murugan, et al.
(författare)
-
Modeling the Structure and Absorption Spectra of Stilbazolium Merocyanine in Polar and Nonpolar Solvents Using Hybrid QM/MM Techniques
- 2010
-
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 114:42, s. 13349-13357
-
Tidskriftsartikel (refereegranskat)abstract
- We have performed Car-Parrinello mixed quantum mechanics/molecular mechanics (CP-QM/MM) calculations for stilbazolium merocyanine (SM) in polar and nonpolar solvents in order to explore the role of solute molecular geometry, solvation shell structure, and different interaction mechanisms on the absorption spectra and its dependence on solvent polarity. On the basis of the average bond length values and group charge distributions, we find that the SM molecule remains in a neutral quinonoid form in chloroform (a nonpolar solvent) while it transforms to a charge-separated benzenoid form in water (a polar solvent). Based on a quantum mechanical/molecular mechanical response technique, with different MM descriptions for the water environment, absorption spectra were obtained as averages over configurations derived from the CP-QM/MM simulations. We show that for SM in water the solute polarization plays a major role in predictions of the lambda(max) and solvatochromic shift and that once this effect is included the contributions from solvent polarization and intermolecular charge transfer become less important. For SM in chloroform and water solvents, we have also performed absorption spectra calculations using a polarizable continuum model in order to address its relative performance compared to the QM/MM response technique. In the case of SM in water, our study supports the notion that, in order to predict accurate absorption spectra and solvatochromic shifts, it is important to use a discrete description of the solvent when it, as in water, is involved in site-specific interaction with the solute molecule. The technique is thus shown to outperform the more conventional polarizable continuum model in predicting the solvatochromic shift.
|
|
| 45. |
- Natarajan Arul, Murugan, et al.
(författare)
-
NMR Spin-Spin Coupling Constants in Polymethine Dyes as Polarity Indicators
- 2012
-
Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 18:37, s. 11677-11684
-
Tidskriftsartikel (refereegranskat)abstract
- Herein, we explore the use of spinspin coupling constants (SSCCs) in merocyanine (MCYNE) dyes as indicators of polarity. For this purpose, we use CarParrinello hybrid quantum mechanics/molecular mechanics (QM/MM) to determine the structures of MCYNE in solvents of different polarity, followed by computations of the SSCCs by using QM/MM linear-response theory. The molecular geometry of MCYNE switches between neutral, cyanine-like, and zwitterionic depending on the polarity of the solvent. This structural variation is clearly reflected in the proton SSCCs in the polymethine backbone, which are highly sensitive to the dielectric nature of the environment; this mechanism can be used as a polarity indicator for different microenvironments. This result is highlighted by computing the SSCCs of the MCYNE probe in the cavity of the beta-lactoglobulin protein. The computed SSCCs clearly indicate a non-polar hydrophobic dielectric nature of this cavity.
|
|
| 46. |
- Norby, Morten S., et al.
(författare)
-
Multipole moments for embedding potentials: Exploring different atomic allocation algorithms
- 2016
-
Ingår i: Journal of Computational Chemistry. - : WILEY-BLACKWELL. - 0192-8651 .- 1096-987X. ; 37:20, s. 1887-1896
-
Tidskriftsartikel (refereegranskat)abstract
- Polarizable quantum mechanical (QM)/molecular mechanics (MM)-embedding methods are currently among the most promising methods for computationally feasible, yet reliable, production calculations of localized excitations and molecular response properties of large molecular complexes, such as proteins and RNA/DNA, and of molecules in solution. Our aim is to develop a computational methodology for distributed multipole moments and their associated multipole polarizabilities which is accurate, computationally efficient, and with smooth convergence with respect to multipole order. As the first step toward this goal, we herein investigate different ways of obtaining distributed atom-centered multipole moments that are used in the construction of the electrostatic part of the embedding potential. Our objective is methods that not only are accurate and computationally efficient, but which can be consistently extended with site polarizabilities including internal charge transfer terms. We present a new way of dealing with well-known problems in relation to the use of basis sets with diffuse functions in conventional atomic allocation algorithms, avoiding numerical integration schemes. Using this approach, we show that the classical embedding potential can be systematically improved, also when using basis sets with diffuse functions, and that very accurate embedding potentials suitable for QM/MM embedding calculations can be acquired. (c) 2016 Wiley Periodicals, Inc.
|
|
| 47. |
- Nørby, Morten Steen
(författare)
-
Extending the capabilities of polarizable embedding through damped linear response theory
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One of the greater challenges of modern quantum chemistry is to meet the growing demands of a detailed description of macro molecules, such as proteins and RNA/DNA. The size of such systems make it an almost impossible task to, from first principle calculations, obtain any detailed information regarding electronic structure. This thesis is focused on development of new computational tools for investigation of electronic transitions within large molecular systems. Central to this is the polarizable embedding (PE) model. For many of these systems electronic transitions are localized to one or a few active sites which in turn will be described by accurate quantum chemical methods. The remaining part of the system, defining the environment, is then treated at a lower level using a classical electrostatic approach. The environment is further incorporated into the Hamiltonian describing the quantum region in an effective manner.The work presented in this thesis covers extensions to the PE model both in the quantum region and in the environmental description. The former, starts by combining the PE model with a damped linear response formalism. This coupling enables the study of electronic processes near resonance and in any frequency range desirable thus covering all from core hole transitions to valence transitions. Another important aspect of this work is the coupling of PE to a polarizable continuum model which allows for inclusion of bulk solvent effects in an effective manner. In addition to these extensions we have further considered alternative ways of acquiring parameters used in the construction of the embedding potential. This is essential for accurate embedding calculations as the embedding potential enters directly in the wave function optimization.
|
|
| 48. |
- Olesiak-Banska, Joanna, et al.
(författare)
-
Revealing Spectral Features in Two-Photon Absorption Spectrum of Hoechst 33342 : A Combined Experimental and Quantum-Chemical Study
- 2013
-
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 117:40, s. 12013-12019
-
Tidskriftsartikel (refereegranskat)abstract
- We present the results of wide spectral range Z-scan measurements of the two-photon absorption (2PA) spectrum of the Hoechst 33342 dye. The strongest 2PA of the dye in aqueous solution is found at 575 nm, and the associated two-photon absorption cross section is 245 GM. A weak but clearly visible 2PA band at similar to 850 nm is also observed, a feature that could not be anticipated from the one-photon absorption spectrum. On the basis of the results of hybrid quantum mechanics/molecular mechanics calculations, we put forward a notion that the long-wavelength feature observed in the two-photon absorption spectrum of Hoechst 33342 is due to the formation of dye aggregates.
|
|
| 49. |
- Olsen, Jogvan Magnus Haugaard, et al.
(författare)
-
Dalton Project : A Python platform for molecular- and electronic-structure simulations of complex systems
- 2020
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 152:21
-
Tidskriftsartikel (refereegranskat)abstract
- The Dalton Project provides a uniform platform access to the underlying full-fledged quantum chemistry codes Dalton and LSDalton as well as the PyFraME package for automatized fragmentation and parameterization of complex molecular environments. The platform is written in Python and defines a means for library communication and interaction. Intermediate data such as integrals are exposed to the platform and made accessible to the user in the form of NumPy arrays, and the resulting data are extracted, analyzed, and visualized. Complex computational protocols that may, for instance, arise due to a need for environment fragmentation and configuration-space sampling of biochemical systems are readily assisted by the platform. The platform is designed to host additional software libraries and will serve as a hub for future modular software development efforts in the distributed Dalton community.
|
|
| 50. |
- Olsen, Stine T., et al.
(författare)
-
Computational assignment of redox states to Coulomb blockade diamonds
- 2014
-
Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084. ; 16:33, s. 17473-17478
-
Tidskriftsartikel (refereegranskat)abstract
- With the advent of molecular transistors, electrochemistry can now be studied at the single-molecule level. Experimentally, the redox chemistry of the molecule manifests itself as features in the observed Coulomb blockade diamonds. We present a simple theoretical method for explicit construction of the Coulomb blockade diamonds of a molecule. A combined quantum mechanical/molecular mechanical method is invoked to calculate redox energies and polarizabilities of the molecules, including the screening effect of the metal leads. This direct approach circumvents the need for explicit modelling of the gate electrode. From the calculated parameters the Coulomb blockade diamonds are constructed using simple theory. We offer a theoretical tool for assignment of Coulomb blockade diamonds to specific redox states in particular, and a study of chemical details in the diamonds in general. With the ongoing experimental developments in molecular transistor experiments, our tool could find use in molecular electronics, electrochemistry, and electrocatalysis.
|
|
