High-accuracy computation of reaction barriers in enzymes

Content Provider	CiteSeerX
Author	Claeyssens, Frederik Harvey, Jeremy N. Man, Frederick R. Mata, Ricardo A. Mulholl, Adrian J. Ranaghan, Kara E. Schütz, Martin Thiel, Stephan Thiel, Walter
Abstract	With the advent of combined quantum mechanics / molecular mechanics (QM/MM) methods, enzymatic reactions have become accessible to theoretical modeling in recent years. QM/MM calculations on enzymes have generally been restricted to semiempirical or density functional QM treatments, which are realistic but of limited accuracy and cannot be improved in a systematic manner. In this work it has for the first time been possible to apply high-level coupled-cluster ab initio electronic structure methods to enzymatic catalysis, in a QM/MM framework. Excellent agreement is obtained between the computed and the experimentally determined activation barriers for two quite different enzymatic reactions, a Claisen rearrangement in chorismate mutase and an electrophilic aromatic substitution in para-hydroxybenzoate hydroxylase. This agreement between experimental and converged theoretical results has broader implications concerning the role of specific dynamic effects in enzyme catalysis that are currently under debate: at least for the two enzymes studied here, such dynamic effects must be small since standard transition state theory describes the reactivity quantitatively. We believe that this paper will be of obvious interest to researchers in the fields of
File Format	PDF
Journal	Angew. Chem
Language	English
Access Restriction	Open
Subject Keyword	Reaction Barrier High-accuracy Computation Qm Mm Systematic Manner Different Enzymatic Reaction Enzyme Catalysis Determined Activation Barrier Dynamic Effect Enzymatic Reaction Theoretical Modeling Qm Mm Calculation Specific Dynamic Effect Standard Transition State Theory Qm Mm Framework Enzymatic Catalysis Density Functional Qm Treatment Excellent Agreement Obvious Interest Para-hydroxybenzoate Hydroxylase Claisen Rearrangement Combined Quantum Mechanic Molecular Mechanic Chorismate Mutase Recent Year Electrophilic Aromatic Substitution First Time Theoretical Result Limited Accuracy
Content Type	Text
Resource Type	Article