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CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals,(More)
Advances in transition state theory and computer simulations are providing new insights into the sources of enzyme catalysis. Both lowering of the activation free energy and changes in the generalized transmission coefficient (recrossing of the transition state, tunneling, and nonequilibrium contributions) can play a role. A framework for understanding(More)
A method is presented for the efficient evaluation of long-range electrostatic forces in combined quantum mechanical and molecular mechanical (QM/MM) calculations of periodic systems. The QM/MM-Ewald method is a linear-scaling electrostatic method that utilizes the particle mesh Ewald algorithm for calculation of point charge interactions of molecular(More)
Combined quantum mechanical and molecular mechanical (QM/MM) calculations and molecular dynamics simulations of bacteriorhodopsin (bR) in the membrane matrix have been carried out to determine the factors that make significant contributions to the opsin shift. We found that both solvation and interactions with the protein significantly shifts the absorption(More)
This review discusses methods for the incorporation of quantum mechanical effects into enzyme kinetics simulations in which the enzyme is an explicit part of the model. We emphasize three aspects: (a) use of quantum mechanical electronic structure methods such as molecular orbital theory and density functional theory, usually in conjunction with molecular(More)
Most enzymatic reactions have very large and remarkably similar apparent second-order rate constants, kcat/KM, at mean values of about 107 M-1 s-1 with kcat in the range of 101000 s-1.1-3 In fact, many reactions approach the diffusional encounter rate at the limited enzyme concentration (<10-5 M) in the cell.4 Wolfenden illustrated the catalytic power of(More)
6.2. Reactive Flux Method 3156 6.3. Model Theories 3156 6.4. Survey 3156 7. Applications 3157 7.1. Yeast Enolase 3157 7.2. Triosephosphate Isomerase 3157 7.3. Methylamine Dehydrogenase 3158 7.4. Alcohol Dehydrogenase 3158 7.5. Thermophilic Alcohol Dehydrogenase 3158 7.6. Haloalkane Dehalogenase 3159 7.7. Dihydrofolate Reductase from E. Coli 3159 7.8.(More)
Protein kinase A (PKA) is a ubiquitous phosphoryl transferase that mediates hundreds of cell signaling events. During turnover, its catalytic subunit (PKA-C) interconverts between three major conformational states (open, intermediate, and closed) that are dynamically and allosterically activated by nucleotide binding. We show that the structural transitions(More)
and valence bond method, solvent effects on S N 2 reaction, and Monte Carlo simulations of chemical reaction in solution. Abstract: A mixed molecular orbital and valence bond (MOVB) method is described in combined ab initio QM/MM simulations of the S N 2 reaction of Cl-+ CH 3 Cl _ ClCH 3 + Cl-in water. The method is based on the construction of individual(More)
A semiempirical AM1/d Hamiltonian is developed to model phosphoryl transfer reactions catalyzed by enzymes and ribozymes for use in linear-scaling calculations and combined quantum mechanical/molecular mechanical simulations. The model, designated AM1/d-PhoT, is parametrized for H, O, and P atoms to reproduce high-level density-functional results from a(More)