title: Virtual high throughput screening in new lead identification.
abstract: Drug discovery continues to be one of the greatest contemporary challenges and rational application of modelling approaches is the first important step to obtain lead compounds, which can be optimised further. Virtual high throughput screening (VHTS) is one of the efficient approaches to obtain lead structures for a given target. Strategic application of different screening filters like pharmacophore mapping, shape-based, ligand-based, molecular similarity etc., in combination with other drug design protocols provide invaluable insights in lead identification and optimization. Screening of large databases using these computational methods provides potential lead compounds, thus triggering a meaningful interplay between computations and experiments. In this review, we present a critical account on the relevance of molecular modelling approaches in general, lead optimization and virtual screening methods in particular for new lead identification. The importance of developing reliable scoring functions for non-bonded interactions has been highlighted, as it is an extremely important measure for the reliability of scoring function. The lead optimization and new lead design has also been illustrated with examples. The importance of employing a combination of general and target specific screening protocols has also been highlighted.
authors.affiliation: Molecular Modeling Group, Organic Chemical Sciences, Indian Institute of Chemical Technology, Tarnaka, Hyderabad- 500 607, India.
authors.forename: Preethi
authors.initials: P
authors.lastname: Badrinarayan
authors.forename: G Narahari
authors.initials: GN
authors.lastname: Sastry
mesh_terms: D000818:Animals; D015195:Drug Design; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry; D010600:Pharmacology
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations