FINDSITE: a threading-based approach to ligand homology modeling.

ABSTRACT: Ligand virtual screening is a widely used tool to assist in new pharmaceutical discovery. In practice, virtual screening approaches have a number of limitations, and the development of new methodologies is required. Previously, we showed that remotely related proteins identified by threading often share a common binding site occupied by chemically similar ligands. Here, we demonstrate that across an evolutionarily related, but distant family of proteins, the ligands that bind to the common binding site contain a set of strongly conserved anchor functional groups as well as a variable region that accounts for their binding specificity. Furthermore, the sequence and structure conservation of residues contacting the anchor functional groups is significantly higher than those contacting ligand

SUBMITTER: Brylinski M 

PROVIDER: S-EPMC2685473 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature