title: Genomes to hits in silico - a country path today, a highway tomorrow: a case study of chikungunya.
abstract: These are exciting times for bioinformaticians, computational biologists and drug designers with the genome and proteome sequences and related structural databases growing at an accelerated pace. The post-genomic era has triggered high expectations for a rapid and successful treatment of diseases. However, in this biological information rich and functional knowledge poor scenario, the challenges are indeed grand, no less than the assembly of the genome of the whole organism. These include functional annotation of genes, identification of druggable targets, prediction of three-dimensional structures of protein targets from their amino acid sequences, arriving at lead compounds for these targets followed by a transition from bench to bedside. We propose here a "Genome to Hits In Silico" strategy (called Dhanvantari) and illustrate it on Chikungunya virus (CHIKV). "Genome to hits" is a novel pathway incorporating a series of steps such as gene prediction, protein tertiary structure determination, active site identification, hit molecule generation, docking and scoring of hits to arrive at lead compounds. The current state of the art for each of the steps in the pathway is high-lighted and the feasibility of creating an automated genome to hits assembly line is discussed.
authors.affiliation: Department of Chemistry, Supercomputing Facility for Bioinformatics & Computational Biology, Indian Institute of Technology, Hauz Khas, New Delhi-110016, India. bjayaram@chemistry.iitd.ac.in
authors.forename: Anjali
authors.initials: A
authors.lastname: Soni
authors.forename: Khushhali M
authors.initials: KM
authors.lastname: Pandey
authors.forename: Pratima
authors.initials: P
authors.lastname: Ray
authors.forename: B
authors.initials: B
authors.lastname: Jayaram
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D002646:Chikungunya virus / Q000187:drug effects / Q000235:genetics*; D003198:Computer Simulation; D016679:Genome, Viral; D017434:Protein Structure, Tertiary; D014764:Viral Proteins / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins