Genomes to Hits In Silico - A Country Path Today, A Highway Tomorrow: A Case Study of Chikungunya
Khushhali M. Pandey,
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.
Keywords: Genome annotation, protein folding, docking and scoring, lead molecule, CHIKV.
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