Abstract

Virtual screening (VS) is the backbone of computational drug discovery workflow, an indispensable component in all drug design programs. It involves a host of modelling techniques from simple similarity search methods to advanced algorithms for finding the accurate bioactive conformation of a molecule to bind to its corresponding target. VS assists drug discovery at every stage from conceptualization to searching for novelty, safety profiles and any known information about molecules at the abstract level from the pool of scientific literature for the discovery of a new molecular entity. Chemoinformatics supports virtual screening at multiple levels during the lead optimization stage by suggesting suitable filters for numerous screenings by utilizing the power of data integration from multiple sources and derived knowledge that is essential for decision support in drug discovery and development. The pharmaceutical industry has benefited tremendously by using the chemoinformatics techniques for designing focused virtual libraries of small organic molecules with desired properties/ affinities. It is therefore timely and pertinent to develop tools, data and emerging methods in chemoinformatics to fully understand their role and applications in virtual screening.  Recently we have developed chemical informatics tools to assist drug discovery by virtual library design, analysis and screening methods on selected case studies. The ligand based virtual screening methods presented include similarity searching, diversity selection, scaffold analysis, library generation, annotation and pharmacophore mapping to find diverse chemotypes from natural products. Structure and fragment based descriptors are compared with machine learning approaches in virtual screening. Text mining approaches involving gleaning of meaningful associations buried under layers of literature data have been successfully shown to act as a fast approach for finding hits in hitherto unknown chemical space. Though the techniques, algorithms computational time etc for virtual screening have increased by leaps and bounds it is surprising that most of the research still focuses on limited number of targets and chemotypes. It will become evident from these studies that a lot of target space is unchartered and a number of diseases have yet to be combated. As more and more authentic data, available with industry, are being made accessible to public at large, the virtual screening efforts will multiply. The details of success story applying chemoinformatics for drug discovery inspired by bioactivity observed from Indian Medicinal plants will be discussed.