Chapter 12: Molecular Simulation in Computer-aided Drug Design: Algorithms and Applications

Molecular simulations have made substantial contributions in the area of drug discovery over the past two decades. These contributions have been facilitated by increases in raw compute power and the availability of high-resolution structures, as well as improvements in general methods and algorithms. In this chapter, the contributions of molecular simulations, in particular molecular dynamics (MD) and Monte Carlo (MC) simulation methods, to the discovery and design of novel therapeutic agents will be discussed. After a brief introduction to drug discovery and pharmacology jargon, the reader is introduced to the concepts of using of molecular simulation to: investigate structure-dynamics-function relationships in clinically-relevant targets, perform predictive ensemble-based virtual screening experiments, estimate free energies of binding and perform hit-to-lead optimization. Advice on presented algorithms and future prospects are also discussed.