| 1. |
- Caldararu, Octav, et al.
(författare)
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Binding free energies in the SAMPL5 octa-acid host–guest challenge calculated with DFT-D3 and CCSD(T)
- 2017
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Ingår i: Journal of Computer-Aided Molecular Design. - : Springer Science and Business Media LLC. - 0920-654X .- 1573-4951. ; 31:1, s. 87-106
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Tidskriftsartikel (refereegranskat)abstract
- We have tried to calculate the free energy for the binding of six small ligands to two variants of the octa-acid deep cavitand host in the SAMPL5 blind challenge. We employed structures minimised with dispersion-corrected density-functional theory with small basis sets and energies were calculated using large basis sets. Solvation energies were calculated with continuum methods and thermostatistical corrections were obtained from frequencies calculated at the HF-3c level. Care was taken to minimise the effects of the flexibility of the host by keeping the complexes as symmetric and similar as possible. In some calculations, the large net charge of the host was reduced by removing the propionate and benzoate groups. In addition, the effect of a restricted molecular dynamics sampling of structures was tested. Finally, we tried to improve the energies by using the DLPNO–CCSD(T) approach. Unfortunately, results of quite poor quality were obtained, with no correlation to the experimental data, systematically too positive affinities (by ~50 kJ/mol) and a mean absolute error (after removal of the systematic error) of 11–16 kJ/mol. DLPNO–CCSD(T) did not improve the results, so the accuracy is not limited by the energy function. Instead, four likely sources of errors were identified: first, the minimised structures were often incorrect, owing to the omission of explicit solvent. They could be partly improved by performing the minimisations in a continuum solvent with four water molecules around the charged groups of the ligands. Second, some ligands could bind in several different conformations, requiring sampling of reasonable structures. Third, there is an indication the continuum-solvation model has problems to accurately describe the binding of both the negatively and positively charged guest molecules. Fourth, different methods to calculate the thermostatistical corrections gave results that differed by up to 30 kJ/mol and there is an indication that HF-3c overestimates the entropy term. In conclusion, it is a challenge to calculate binding affinities for this octa-acid system with quantum–mechanical methods.
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| 2. |
- Chalupsky, Jakub, et al.
(författare)
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Multireference ab initio calculations on reaction intermediates of the multicopper oxidases
- 2006
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 1520-510X .- 0020-1669. ; 45:26, s. 11051-11059
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Tidskriftsartikel (refereegranskat)abstract
- The multicopper oxidases (MCOs) couple the four-electron reduction of dioxygen to water with four one-electron oxidations of various substrates. Extensive spectroscopic studies have identified several intermediates in the MCO catalytic cycle, but they have not been able to settle the structures of three of the intermediates, viz. the native intermediate (NI), the peroxy intermediate (PI), and the peroxy adduct (PA). The suggested structures have been further refined and characterized by quantum mechanical/molecular mechanical (QM/MM) calculations. In this paper, we try to establish a direct link between theory and experiment, by calculating spectroscopic parameters for these intermediates using multireference wave functions from the multistate CASPT2 and MRDDCI2 methods. Thereby, we have been able to reproduce low-spin ground states (S = 0 or S = 1/2) for all the MCO intermediates, as well as a low-lying (similar to 150 cm(-1)) doublet state and a doublet-quartet energy gap of similar to 780 cm(-1) for the NI. Moreover, we reproduce the zero-field splitting (similar to 70 cm(-1)) of the ground E-2 state in a D-3 symmetric hydroxy-bridged trinuclear Cu(II) model of the NI and obtain a quantitatively correct quartet-doublet splitting (164 cm(-1)) for a mu 3-oxo-bridged trinuclear Cu( II) cluster. All results support the suggestion that the NI has an O-2-atom in the center of the trinuclear cluster, whereas both the PI and PA have an O-2(2-) ion in the center of the cluster, in agreement with the QM/MM results and spectroscopic measurements.
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| 3. |
- Vancoillie, Steven, et al.
(författare)
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Multireference Ab Initio Calculations of g tensors for Trinuclear Copper Clusters in Multicopper Oxidases.
- 2010
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 114:22, s. 7692-7702
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Tidskriftsartikel (refereegranskat)abstract
- EPR spectroscopy has proven to be an indispensable tool in elucidating the structure of metal sites in proteins. In recent years, experimental EPR data have been complemented by theoretical calculations, which have become a standard tool of many quantum chemical packages. However, there have only been a few attempts to calculate EPR g tensors for exchange-coupled systems with more than two spins. In this work, we present a quantum chemical study of structural, electronic, and magnetic properties of intermediates in the reaction cycle of multicopper oxidases and of their inorganic models. All these systems contain three copper(II) ions bridged by hydroxide or O(2-) anions and their ground states are antiferromagnetically coupled doublets. We demonstrate that only multireference methods, such as CASSCF/CASPT2 or MRCI can yield qualitatively correct results (compared to the experimental values) and consider the accuracy of the calculated EPR g tensors as the current benchmark of quantum chemical methods. By decomposing the calculated g tensors into terms arising from interactions of the ground state with the various excited states, the origin of the zero-field splitting is explained. The results of the study demonstrate that a truly quantitative prediction of the g tensors of exchange-coupled systems is a great challenge to contemporary theory. The predictions strongly depend on small energy differences that are difficult to predict with sufficient accuracy by any quantum chemical method that is applicable to systems of the size of our target systems.
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