107 Genomes to hit molecules In Silico: a country path today, a highway tomorrow: a case study of Chikungunya

Abstract

The growing genomic and proteomic sequence/structural databases trigger high expectations for a rapid and successful treatment of diseases and disorders. In the current biological information, rich and functional knowledge, poor scenario, the feasibility of creating an automated genomes to hits (G2H) assembly line in order to cut down the cost and time in drug discovery is discussed. The G2H computational pathway involves several challenging research areas viz. functional annotation of genomes, identification of druggable targets, prediction of three-dimensional structures of protein targets from their amino acid sequences, and hit molecule generation for these targets followed by a transition from bench to bedside. We describe the ‘G2H In Silico’ strategy (called Dhanvantari), and illustrate it on Chikungunya virus (CHIKV). G2H is a novel pathway incorporating, a series of steps such as gene prediction (Chemgenome), protein tertiary structure determination (Bhageerath), automated active site identification, rapid hit molecule generation followed by atomic level docking and scoring of hits to arrive at lead compounds (Sanjeevini). The current state of the art for each of the steps in the pathway will be highlighted and the results will be presented and discussed.