Dynamic Force Field Models: Molecular Dynamics Simulations of Human Carbonic Anhydrase II Using a Quantum Mechanical/Molecular Mechanical Coupled Potential

Hartsough, David S.; Merz, Kenneth M. Jr.

doi:10.1021/j100028a030

Cited by 67 publications

(77 citation statements)

References 19 publications

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“…The development of combined quantum mechanical/ molecular mechanics (QM/MM) computational models (e.g., [14,131,[134][135][136][137][138][139][140]) that allow enzymatic reactions to be simulated provided a way for quantifying the main factors that contribute to enzyme catalysis. QM/MM studies, including those conducted by the empirical valence bond (EVB) method [132], helped to establish the proposal [141] that the electrostatic effects of preorganized active sites play a major role in stabilizing the transition states of enzymatic reactions [142].…”

Section: Enzyme Catalysismentioning

confidence: 99%

Electrostatics of Proteins: Principles, Models and Applications

Braun‐Sand¹,

Warshel²

2005

Protein Folding Handbook

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Section: Enzyme Catalysismentioning

confidence: 99%

Electrostatics of Proteins: Principles, Models and Applications

Braun‐Sand¹,

Warshel²

2005

Protein Folding Handbook

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“…Because of the incomplete transferability of potential energy models between different types of physical systems of interest, there is not likely to be a universal model that will work in all systems, at least for some subdomains of the various systems. As purely quantum simulations are still beyond the reach of present computer power despite the efforts toward this direction, 28 more empirical modeling of the CA II active site is therefore necessary in order to obtain results from molecular dynamics computer simulations. The usual empirical approach to modeling biophysical systems relies on a combination of theoretical ab initio calculations and fitting to experimentally determined properties.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulations of human carbonic anhydrase II: Insight into experimental results and the role of solvation

Voth

1998

Proteins

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In this paper, the carbonic anhydrase II (CA II) enzyme active site is modeled using ab initio calculations and molecular dynamics simulations to examine a number of important issues for the enzyme function. It is found that the Zn2+ ion is dominantly tetrahedrally coordinated, which agrees with X-ray crystallographic studies. However, a transient five-fold coordination with an extra water molecule is also found. Studies of His64 conformations upon a change in the protonation states of the Zn-bound water and the His64 residue also confirm the results of an X-ray study which suggest that the His64 conformation is quite flexible. However, the degree of water solvation is found to affect this behavior. Water bridge formation between the Zn-bound water and the His64 residue was found to involve a free energy barrier of 2-3 kcal/mol and an average lifetime of several picoseconds, which supports the concept of a proton transfer mechanism through such a bridge. Mutations of various residues around the active site provide further insight into the corresponding experimental results and, in fact, suggest an important role for the solvent water molecules in the CA II catalytic mechanism.

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“…The union of molecular mechanics/dynamics and quantum mechanics is being intensely studied in several laboratories (53)(54)(55)(56). These techniques make possible the introduction of time-dependent phenomena such as polarization and charge exchange and are thus more realistic in accommodating actual electronic behavior; new general tools that make available quantum mechanical dynamics should appear soon.…”

Section: Resultsmentioning

confidence: 99%

Selected new developments in computational chemistry.

Darden

Bartolotti

Pedersen

1996

Environ Health Perspect

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Molecular dynamics is a general technique for simulating the time-dependent properties of molecules and their environments. Quantum mechanics, as applied to molecules or clusters of molecules, provides a prescription for predicting properties exactly (in principle). It is reasonable to expect that both will have a profound effect on our understanding of environmental chemistry in the future. In this review, we consider several recent advances and applications in computational chemistry. Environ Health Perspect 104(Suppl 1): 69-74 (1996)

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Dynamic Force Field Models: Molecular Dynamics Simulations of Human Carbonic Anhydrase II Using a Quantum Mechanical/Molecular Mechanical Coupled Potential

Cited by 67 publications

References 19 publications

Electrostatics of Proteins: Principles, Models and Applications

Electrostatics of Proteins: Principles, Models and Applications

Molecular dynamics simulations of human carbonic anhydrase II: Insight into experimental results and the role of solvation

Selected new developments in computational chemistry.

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