Empirical valence-bond method

This chapter presents the implementaiton and applicable of a QM-MM method for studying enzyme-catalyzed reactions. The application of QM-MM methods to study solution-phase reactions has been reviewed elsewhere [44]. Similiarly, empirical valence bond methods, which have been successfully applied to studying enzymatic reactions by Warshel and coworkers [19,45], are not covered in this chapter. 

A method that has certain connections with QM/MM techniques even if it does not usually involve simultaneous evaluation of QM and MM operators during a particular calculation is the empirical valence bond method (EVB Warshel and Weiss 1980). At the heart of the EVB method is the notion diat arbitrarily complex reactions may be modeled as the influence of a surrounding environment on a fundamental process that may be represented by some combination of valence bond resonance structures. For example, tlie proton transfer from one water molecule to another may, at any point along the reaction path, be envisaged as involving some admixture of tlie two VB wave functions corresponding formally to... 

W. Wu, S. J. Zhong, S. Shaik, Chem. Phys. Lett. 292, 7 (1998). VBDFT(s) A Hiickel-Type Semi-empirical Valence Bond Method Scaled to Density Functional Energies. Application to Linear Polyenes. 

One of the first attempts to introduce the solvent effect in a VB analysis for the comprehension of a chemical reaction in solution has been given by Warshel and Weiss [10]. These authors introduced the Empirical Valence Bond method (EVB) for the modeling of proton transfer processes in enzymatic reactions in aqueous environment. 

Warshel and collaborators (Warshel and Sussman, 1986 Warshel et al., 1988) developed the empirical valence bond method for obtaining free-energy differences and activation free energies. The effects of Gly-to-Ala mutations in trypsin were accurately simulated. This method was earlier applied to calculation of the potential surface for general acid catalysis of a disaccharide in solution and bound to lysozyme (Warshel and Weiss, 1980). 

Empirical Valence Bond Methods. - To examine some important questions relating to enzyme action (e.g. to analyse the causes of catalysis, i.e. why an enzymic reaction proceeds faster than the equivalent, uncatalysed reaction in solution), it is necessary to use a method that not only captures the essential details of the chemical reaction, but also includes the explicit effects of the enzyme and solvent enviroment. One notable method in this area is the empirical valence bond (EVB) model.143 In the empirical valence bond approach, resonance structures (for example ionic and covalent resonance forms)... 

QM/MM (AM1/CHARMM) or empirical valence bond methods, respectively164 168), for forcing the conformation of chorismate in solution into the more restricted conformation found in the enzyme. This equates to a catalytic benefit of only around 40-55% of the total AA G between enzyme and solvent. The good agreement between these findings, which applied completely different theoretical methods, is striking and suggests that this is a reliable result. 

Diatomics-in-Molecules (DIM) Method Semi-Empirical Valence-Bond Methods Approximate Pseudo-Potential Theories... 

These problems were attacked through simulation by Keirstead, Wilson, and Hynes. 232 jhg techniques they used are similar to those used in the simulation of electron-transfer reactions by Zichi et al. and are related to the empirical valence bond method of WarsheP discussed previously. The technique involved constructing an overall Hamiltonian from the Hamiltonians for the covalent, H ov> and ionic, electronic states of the t-butyl chloride... 

Type Semi-empirical Valence Bond Method Scaled to Density Functional Energies. Applications to Linear Polyene. 

Wei W, Zhong SJ, Shark S (1998) VBDFT(s) a Huckel-type semi-empirical valence bond method scaled to density functional energies. Application to linear polyenes. Chem Phys Lett 292 7-14... 

Wu W et al (2001) VBDFT(s) - a semi-empirical valence bond method application to linear polyenes containing oxygen and nitrogen heteroatoms. Phys Chem Chem Phys 3 5459-5465... 

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