Empirical valence bond approach

In 1976 Warshel and Levitt introduced the idea of a hybrid QM/MM method [23] that treated a small part of a system (e.g., the solute) using a quantum mechanical representation, while the rest of the system, which did not need such a detailed description (e.g., the solvent) was represented by an empirical force field. These hybrid methods, in particular the empirical valence bond approach, were then used to study a wide variety of reactions in solution. The combined QM/MM methods use the MM method with the potential calculated ab initio [24]. 

Multistate Empirical Valence Bond Approach to a Polarizable and Flexible Water Model. 

Warshel, A. and Weiss, R, M. (1980) An Empirical Valence Bond Approach for Computing Reactions in Solutions and in Enzymes, J. Am. Chem. Soc. 102, 6218-6226. 

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)... 

Even greater speed enhancement can be achieved through the use of empirical quantum mechanically based schemes. A good example of this in the mixed quantum/classical methodology developed by Warshel and coworkers. This method uses an empirical valence bond approach to treat the quantum motif and hence is extremely inexpensive (commutationally) to include. Warshel has illustrated a number of qualitative ideas using these methods [48]. However, a key aspect to such an approach is the ability to adequately specify the appropriate resonance forms for the ionic and covalent species. 

The key issue of incorporating solvent effects in the quantum mechanical calculation has not been solved satisfactorily in MC and molecular dynamics studies overviewed above. Warshefs empirical valence bond approach, van Duijnen s direct reaction field method, and Tapia s ISCRF theory, by including these solvent effects, are steps forward in this direction. Although the key theoretical issue cannot be considered satisfactorily solved, the applications made are most interesting. 

In this chapter, we have reviewed the basic elements of the empirical valence bond approach for simulating chemical reactions in enzymes and in solutions. The alternative molecular orbital treatment has also been outlined and the differences between the two approaches discussed. As far as calculations of free energy profiles in enzymes is concerned, we conclude that the former method is far more convenient and accurate since it allows for the incorporation of experimental information about the relevant energy surfaces, e.g. in aqueous solution. This point deserves to be emphasised in view of the common belief that only ab initio quantum calculations (as opposed to those based on some degree of empirical parametrisation) can provide accurate answers to chemical questions (for a related discussion, see [24]) this is particularly untrue for reactions in liquid phases and in proteins. As is the case with semi-empirical MO schemes, the EVB method is also semi-empirical but it is parametrised on information that is more relevant as far as bond breaking/forming processes in condensed phases are concerned. 

Warshel A, Weiss RM (1980) An empirical valence bond approach for comparing reactions in solutions and in enzymes. J Am Chem Soc 102 6218... 

Very often a specific semiempirical MO method was adopted to represent Hqu and a specific MM method was used for //mm and the coupling term / qm-mm introduced additional empirical parameters to allow the combined energy to reproduce experiments. Thus they are specific to the MO method and the MM method adopted at the initial definition of the method. The empirical valence bond approach has also been combined with MM for more complex systems. There have been other approaches attempting to incorporate different procedures which show the importance of combining these methods and the difficulty in doing so. Numerous QM/MM studies have been made in the past, including various versions, some applications, " the treatment of charges, application to zeolites and biochemistry, molecular dynamics, and solvent effects. These variations of the so-called QM/MM methods are treated in separate articles. 

A. Semi-empirical Valence Bond Approaches for Benzenoid Hydrocarbons... 

Sierka M and Sauer J (2000), Finding transition structures in extended systems a strategy based on a combined quantum mechanics-empirical valence bond approach , J. Chem. Phys., 112(16), 6983-6996. 

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