New method for the assessment of all drug-like pockets across a structural genome.
With the increasing wealth of structural information available for human pathogens, it is now becoming possible to leverage that information to aid in rational selection of targets for inhibitor discovery. We present a methodology for assessing the drugability of all small-molecule binding pockets in a pathogen. Our approach incorporates accurate pocket identification, sequence conservation with a similar organism, sequence conservation with the host, and structure resolution. This novel method is applied to 21 structures from the malarial parasite Plasmodium falciparum. Based on our survey of the structural genome, we selected enoyl-acyl carrier protein reductase (ENR) as a promising candidate for virtual screening based inhibitor discovery.
Nicola
George
G
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
Smith
Colin A
CA
Abagyan
Ruben
R
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D015195:Drug Design; D016678:Genome / Q000235:genetics*; D006801:Humans; D010963:Plasmodium falciparum / Q000737:chemistry; D020543:Proteome / Q000737:chemistry*; D015800:Protozoan Proteins / Q000737:chemistry*
D020543:Proteome; D015800:Protozoan Proteins