Multicoordinate Driven Method for Approximating Enzymatic Reaction Paths:  Automatic Definition of the Reaction Coordinate Using a Subset of Chemical Coordinates

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Molecules, spectroscopy, kinetics, environment, & general theory, 2006-01, Vol.110 (2), p.772-778
• Main Authors: Berente, Imre, Náray-Szabó, Gábor
• Format: Article
• Language: English
• Subjects: Binding Sites; Enzymes - chemistry; Enzymes - metabolism; Hydrolysis; Methods; Models, Chemical; Pyrophosphatases - chemistry; Pyrophosphatases - metabolism; Water - chemistry
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/jp054116z

We present a generalization of the reaction coordinate driven method to find reaction paths and transition states for complicated chemical processes, especially enzymatic reactions. The method is based on the definition of a subset of chemical coordinates; it is simple, robust, and suitable to calculate one or more alternative pathways, intermediate minima, and transition-state geometries. Though the results are approximate and the computational cost is relatively high, the method works for large systems, where others often fail. It also works when a certain reaction path competes with others having a lower energy barrier. Accordingly, the procedure is appropriate to test hypothetical reaction mechanisms for complicated systems and provides good initial guesses for more accurate methods. We present tests on a number of simple reactions and on several complicated chemical transformations and compare the results with those obtained by other methods. Calculation of the reaction path for the enzymatic hydrolysis of the substrate by dUTPase for an active-site model with 85 atoms, including several loosely bound water molecules, indicates that the method is feasible for the study of enzyme mechanisms.