Specialized methods for improving ergodic sampling using molecular dynamics and Monte Carlo simulations

Abstract

In this chapter we have presented an eclectic set of enhanced sampling methods to address the problem of conformational sampling, which is one of several key factors for a successful free energy estimation. We have outlined the problem facing simulations of complex systems, that of broken ergodicity, and have introduced a metric, the ergodic measure, which can be used as a (necessary) criterion to assess whether sampling is thorough. We have then reviewed several established, as well as newly developed, methods for classical systems. Last, calculations of quantum free energy in the context of an isomorphism to classical systems has been addressed, stressing the utility of developing ad hoc enhanced sampling methods for this case as well. While all enhanced sampling methods, reviewed here or not, are good strategies in themselves because they improve convergence in the calculation of equilibrium averages, it is important to note that there is no 'best' method. Rather various methods may be good for various systems or reasons.We hope to have left the reader with the conviction that it is often the case that ad hoc modification of existing strategies, or newly devised ones, can bring about worthwhile improvements to aid the calculation of thermodynamical observables. © 2007 Springer-Verlag.