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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)
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)
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)
Molecular dynamics simulations using a combined QM/MM potential have been performed to study the catalytic mechanism of human cathepsin K, a member of the papain family of cysteine proteases. We have determined the two-dimensional free energy surfaces of both acylation and deacylation steps to characterize the reaction mechanism. These free energy profiles(More)
The generalized hybrid orbital (GHO) method has previously been formulated for combining molecular mechanics with various levels of quantum mechanics, in particular semiempirical neglect of diatomic differential overlap theory, ab initio Hartree-Fock theory, and self-consistent charge density functional tight-binding theory. To include electron-correlation(More)
The generalized hybrid orbital (GHO) method provides a way to combine quantum mechanical (QM) and molecular mechanical (MM) calculations on a single molecular system or supramolecular assembly by providing an electrostatically stable connection between the QM portion and the MM portion. The GHO method has previously been developed for semiempirical(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)