| 1. |
- De Vico, Luca, et al.
(författare)
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The ozone ring closure as a test for multi-state multi-configurational second order perturbation theory (MS-CASPT2)
- 2008
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Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614. ; 461:1-3, s. 136-141
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Tidskriftsartikel (refereegranskat)abstract
- The open and closed forms of ozone and the path connecting them through a transition state, in C-2v symmetry, are explored using the multi-state, multi-configurational second order perturbative method, MS-CASPT2. It is demonstrated that, by using an ANO-L triple-zeta basis set, it is possible to set up an active space able to describe the otherwise troublesome transition state region. Both a conical intersection and a near degeneracy region between the 1(1)A(1) and 2(1)A(1) states are located in the vicinity of the transition state. The relative position of the intersection and the transition state are discussed. (c) 2008 Elsevier B. V. All rights reserved.
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| 2. |
- Heimdal, Jimmy, et al.
(författare)
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Protonation of the proximal histidine ligand in heme peroxidases.
- 2008
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 112:8, s. 2501-2510
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Tidskriftsartikel (refereegranskat)abstract
- The heme peroxidases have a histidine group as the axial ligand of iron. This ligand forms a hydrogen bond to an aspartate carboxylate group by the other nitrogen atom in the side chain. The aspartate is not present in the globins and it has been suggested that it gives an imidazolate character to the histidine ligand. Quantum chemical calculations have indicated that the properties of the heme site strongly depend on the position of the proton in this hydrogen bond. Therefore, we have studied the location of this proton in all intermediates in the reaction mechanism, using a set of different quantum mechanical and combined experimental and computational methods. Quantum refinements of a crystal structure of the resting FeIII state in yeast cytochrome c peroxidase show that the geometric differences of the two states are so small that it cannot be unambiguously decided where the proton is in the crystal structure. Vacuum calculations indicate that the position of the proton is sensitive to the surroundings and to the side chains of the porphyrin ring. Combined quantum and molecular mechanics (QM/MM) calculations indicate that the proton prefers to reside on the His ligand in all states in the reaction mechanism of the peroxidases. QM/MM free energy perturbations confirm these results, but reduce the energy difference between the two states to 12-44 kJ/mol.
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| 3. |
- Jensen, Kasper P., et al.
(författare)
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A comparison of the tetrapyrrole cofactors in nature and their tuning by axial ligands
- 2008
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Ingår i: Computational modeling for homogeneous and enzymatic catalysis. - 9783527318438 ; , s. 27-56
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter illustrates how quantum chemical calculations can be used to elucidate structural and functional aspects of tetrapyrrole cofactors, focusing on porphyrins, cobalamins, coenzyme F430, and chlorophyll. A particular emphasis is put on the biochemical significance of axial ligands, which can tune the function of the tetrapyrroles. With the use of quantum chemical calculations, it is possible to draw important conclusions regarding aspects of tetrapyrroles that could not otherwise be accessed. The results show that the general reactivity is mainly determined by the metal and the tetrapyrrole ring system, whereas the electronic structure and reactivity are tuned by the choice of axial ligands, providing a unique insight into the design of cofactors in nature.
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| 4. |
- Kaukonen, Markus, et al.
(författare)
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Proton transfer at metal sites in proteins studied by quantum mechanical free-energy perturbations
- 2008
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 4:6, s. 985-1001
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Tidskriftsartikel (refereegranskat)abstract
- Catalytic metal sites in enzymes frequently have second-sphere carboxylate groups that neutralize the charge of the site and share protons with first-sphere ligands. This gives rise to an ambiguity concerning the position of this proton, which has turned out to be hard to settle with experimental, as well as theoretical, methods. We study three such proton-transfer reactions in two proteins and show that, in [Ni,Fe] hydrogenase, the bridging Cys-546 ligand is deprotonated by His-79, whereas in oxidized copper nitrite reductase, the His-100 ligand is neutral and the copper-bound water molecule is deprotonated by Asp-98. We show that these reactions strongly depend on the electrostatic interactions with the surrounding protein and solvent, because there is a large change in the dipole moment of the active site (2-6 D). Neither vacuum quantum mechanical (QM) calculations with large models, a continuum solvent, or a Poisson-Boltzmann treatment of the surroundings, nor combined QM and molecular mechanics (QM/MM) optimizations give reliable estimates of the proton-transfer energies (mean absolute deviations of over 20 kJ/mol). Instead, QM/MM free-energy perturbations are needed to obtain reliable estimates of the reaction energies. These calculations also indicate what interactions and residues are important for the energy, showing how the quantum system may be systematically enlarged. With such a procedure, results with an uncertainty of similar to 10 kJ/mol can be obtained, provided that a proper QM method is used.
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| 5. |
- Kaukonen, Markus, et al.
(författare)
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QM/MM-PBSA method to estimate free energies for reactions in proteins
- 2008
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 112:39, s. 12537-12548
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a method to estimate free energies of reactions in proteins, called QM/MM-PBSA. It estimates the internal energy of the reactive site by quantum mechanical (QM) calculations, whereas bonded, electrostatic, and van der Waals interactions with the surrounding protein are calculated at the molecular mechanics (MM) level. The electrostatic part of the solvation energy of the reactant and the product is estimated by solving the Poisson-Boltzmann (PB) equation, and the nonpolar part of the solvation energy is estimated from the change in solvent-accessible surface area (SA). Finally, the change in entropy is estimated from the vibrational frequencies. We test this method for five proton-transfer reactions in the active sites of [Ni,Fe] hydrogenase and copper nitrite. reductase. We show that QM/MM-PBSA reproduces the results of a strict QM/MM free-energy perturbation method with a mean absolute deviation (MAD) of 8-10 kJ/mol if snapshots from molecular dynamics simulations are used and 4-14 kJ/mol if a single QM/MM structure is used. This is appreciably better than the original QM/MM results or if the QM energies are supplemented with a point-charge model, a self-consistent reaction field, or a PB model of the protein and the solvent, which give MADs of 22-36 kJ/mol for the same test set.
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