Using Molecular Simulations to Probe Pharmaceutical Materials

Evolved through the past 60 years, molecular simulations have become one of the most important analytical tools in many theoretical and applied scientific disciplines. This paper provides a brief introduction to molecular simulations as a means of addressing important scientific questions of interest to pharmaceutical scientists. The focus is on fundamental questions such as: (1) Why do simulations work? (2) How to simulate? (3) How to make the results of simulations “real?” (4) Where can simulations be applied? To demonstrate the fundamental rationale of molecular simulations, three perspectives, thermodynamics, statistical mechanics, and general statistics, are compared. The concept of stochasticity is introduced, followed by a brief account of the two major methods used in simulations, molecular dynamics and Monte Carlo simulations. A brief discussion is then given on force fields to indicate their central importance. To facilitate the discussion about possible applications to pharmaceutical systems, the characteristics of molecular simulations are first compared with those of laboratory experiments. Case studies are then introduced to demonstrate the strengths of simulations. Some frequently encountered questions also are presented and discussed.