Enzymatic Reaction and Chemisorption on Surfaces

The reaction path of the enzyme TIM was characterized by energy minimizations using the combined AMl/CHARMM potential.28 285 in that study, the substrate and the catalytic side chains of His-95 and Glu-165 were treated quantum mechanically, and all other molecules in a stochastic boundary system (a 16-A sphere) were treated by the empirical CHARMM potential. The entire system consisted of 1250 protein atoms and 100 water molecules. An energy decomposition method was used to locate residues important in catalysis. In addition to the large energy contributions from conserved residues, other amino acids make smaller contributions, but their cumulative effect is significant. Interestingly, a number of residues far from the active site also have sizable effects on the enzyme s catalytic ability.284 

Vasilyev studied the process leading to the formation of the tetrahedral intermediate in the acylation step in acetylcholinesterase.286 A combined PM3/ OPLS potential was developed and used to determine the reaction path. In comparison with the gas phase process, the enzyme environment drastically changes the flow of the reaction, lowering the activation energy by 27 kcal/mol. 

In this review, we have summarized the methodologies and applications of combined QM/MM potentials in statistical mechanical Monte Carlo and molecular dynamics simulations. The method is particularly useful for systems that cannot be appropriately described by molecular mechanics force fields and 

It is of particular interest and importance to incorporate the solvent quantum effects into condensed phase simulations. Recently, Warshel and coworkers attempted to represent the quantum effect of the solvent by a frozen density functional method.102 

Reichardt, Solvents and Solvent Effects in Organic Chemistry, VCH Publishers, New York, 1990. 

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