Abstract

Discovery of new therapeutics is a very challenging, expensive and timeconsuming process. With the number of approved drugs declining steadily combined with increasing costs, a rational approach is needed to facilitate, expedite and streamline the drug discovery process. In this regard computational methods are playing increasingly important roles, largely assisted by developments in algorithms and greatly increased computer power. With in silico methods playing key roles in the discovery of growing numbers of marketed drugs, nowadays use of computational tools has become an integral part of most drug discovery programs. Computational tools can be applied at different stages: from target selection through identification of hits to optimization. In this chapter we aim to provide an overview of major tools that have been developed and are routinely being used in the search of novel drug candidates. In addition, we present recent advances, especially in the application of physics-based simulation methodologies, in the drug discovery process for the development of improved therapeutics.