%0 Journal Article
%T Applications of Potential Energy Surfaces in the Study of Enzymatic Reactions
%A Eric A. C. Bushnell
%A WenJuan Huang
%A James W. Gauld
%J Advances in Physical Chemistry
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/867409
%X From a generated PES, one can determine the relative energies of species involved, the sequence in which they occur, and the activation barrier(s) associated with individual steps or the overall mechanism. Furthermore, they can provide more insights than a simple indication of a path of sequential mechanistic structures and their energetic relationships. The investigation into the activation of O2 by alpha-ketoglutarate-dependent dioxygenase (AlkB) clearly shows the opportunity for spin inversion, where one can see that the lowest energy product may be formed via several possible routes. In the investigation of uroporphyrinogen decarboxylase III (UROD), the use of QM/MM methods allowed for the inclusion of the anisotropic protein environment providing greater insight into the rate-limiting barrier. Lastly, the mechanism of 6-phospho-¦Á-glucosidase (GlvA) was discussed using different active site models. In particular, a continuum model PES was compared to the gas-phase PES. 1. Introduction For a chemical reaction, enzymatic or nonenzymatic, the reactants, intermediates, and products all exist on a multidimensional surface. With this surface, a reaction is perfectly described by the statistical average of all possible paths from reactants to products via all possible intermediates [1]. However, a system with N atoms would require computing a (3N-6)-dimensional surface. Hence, if X number of points are to be computed for each of the (3N-6) dimensions, then calculations must be done [1]. Thus, such an undertaking is usually only computationally feasible for chemical models that consist of a few atoms. In contrast, studies on enzymatic mechanisms often necessarily require large chemical models consisting of important active site functional groups and cofactors and the substrate. Indeed, the cluster-based approach for investigating biochemical reactions typically use chemical models containing 200 atoms or more [2]. Thus, for such systems, it is impossible to determine the complete PES. Instead, a ˇ°sliceˇ± of the surface is typically constructed that involves only two coordinates, energy and reaction coordinate, and is commonly referred to as the PES [3]. The use and applicability of such ˇ°reduced-dimensionalityˇ± PESs reflects the fact that chemists and biochemists are usually only interested in key, mechanistically relevant structures including, for example, the (i) isolated reactants, (ii) reactive complex, (iii) transition structures (TS), (iv) intermediate(s), (v) product complex, and (vi) the separated products (Figure 1) [1]. It is noted that in general,
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