Computational Resources for Protein Modelling and Drug Discovery Applications

The design of new medications is an intensive, time-consuming and costly process. Over the years, a rational approach that exploits the structural knowledge of a biological target has led to many successes. This procedure can be expedited using computer-aided modelling techniques. The structure-based approach to drug design relies on knowing the three-dimensional structure of the target macromolecule. If an experimental structure has not been determined yet, a good approximation of the protein target structure can be obtained through computational modelling, provided that some structures of its homologues are available to serve as templates. The vast majority of drugs currently on the market act by disrupting the interaction between a protein and its physiological ligand(s). Hence, once a molecular model is available, the next step is to identify and study its putative ligand-binding sites. Molecular “docking” may then be performed in silico to predict the modes of interaction between the ligand and the target. In this review, a list of computational resources for structure-based drug design has been compiled. It is hoped that readers who do not have much experience will be equipped with the appropriate tools to make a first attempt at protein modelling and in silico ligand docking exercises.