The Empirical Valence Bond (EVB) Method

The empirical valence bond (EVB) model is a powerful conceptual and practical tool for studies of reactions of complex systems, ranging from reactions of large molecules to chemical processes in solutions and in enzymes. This method that can be viewed as an extension of force-field approaches to chemical reactivity is related here to other hybrid quantum mechanical/molecular mechanics (QM/MM) methods and to other approaches. The review starts by pointing out the relationship between the EVB and early VB concepts. It is noted that while the VB models were developed for studies of chemical bonding in small molecules, the EVB models have provided a general and uniform way of simulating chemical reactions in large molecules and molecules in any environment. The use of the EVB approach in modeling chemical reactions is reviewed, emphasizing the effectiveness of the method in studies of enzyme catalysis. The advantages of the EVB approach are also considered, pointing out the usefulness of the analytical form of this method and its crucial importance for molecular dynamics simulations and free energy calculations of processes in condensed phases. Finally, the current proliferation of the EVB approach and its emergence under different names is discussed, clarifying the relationship between the different EVB–type models. Keywords: valence bond; solvation; QM/MM; EVB; enzyme catalysis; enzyme mechanisms; force-fields; reactions in solutions; FEP of chemical reactions; LFER; transition state search