Empirical Classical Force Fields for Molecular Systems

Abstract

With the continuing increase of the power of computers, the past decades have seen a rapid increase in the number, performance and accuracy of theoretical computational methods in chemistry (van Gunsteren et al., 1989 ff, Lipkowitz & Boyd, 1990ff). One can distinguish three major classes of methods for the theoretical study of molecular properties, listed in order of decreasing computational expenses: (i) ab initio molecular-orbital methods (Hehre et al., 1986), (ii) semi-empirical molecular-orbital methods (Zerner, 1991), and (iii) empirical classical force-field methods. Since the available computing resources are most often the true limiting factor to numerical calculations, it has become clear that there is no universal method able to solve all possible problems, but that one should rather select the method that is the most suitable to a problem of interest. The properties of the observable (s) and system under consideration that will, together with the available computing power, largely determine which type of method can be used are (van Gunsteren & Berendsen, 1990): (i) the required system size, (ii) the required volume of conformational space that has to be searched or sampled (in terms of dynamics: the required time-scale), (iii) the required resolution in terms of particles (determined by the smallest entity, subatomic particle, atom, or group of atoms, treated explicitly in the model), and (iv) the required energetical accuracy of the interaction function. These requirements may be incompatible, in which case the observable cannot be computed adequately with the currently available computer resources (van Gunsteren et al., 1995b). When requirements (i) and (ii) are in conflict with requirement (iii), this conflict may be resolved by the design of hierarchical or hybrid models, where only the relevant degrees of freedom are treated with a more expensive, higher resolution method. This is often done, for example, in the study of acid- or base-catalysed, organic or enzymatic reactions in the bulk phase (Warshel, 1991, Field, 1993, Whitnell & Wilson, 1993, Liu et al., 1996a).