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J Mol Graph Model. 2003 Jan;21(4):289-307.

LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites.

Author information

  • 1Accelrys Inc., 9685 Scranton Road, San Diego, CA 92121, USA. venkat@accelrys.com

Abstract

We present a new shape-based method, LigandFit, for accurately docking ligands into protein active sites. The method employs a cavity detection algorithm for detecting invaginations in the protein as candidate active site regions. A shape comparison filter is combined with a Monte Carlo conformational search for generating ligand poses consistent with the active site shape. Candidate poses are minimized in the context of the active site using a grid-based method for evaluating protein-ligand interaction energies. Errors arising from grid interpolation are dramatically reduced using a new non-linear interpolation scheme. Results are presented for 19 diverse protein-ligand complexes. The method appears quite promising, reproducing the X-ray structure ligand pose within an RMS of 2A in 14 out of the 19 complexes. A high-throughput screening study applied to the thymidine kinase receptor is also presented in which LigandFit, when combined with LigScore, an internally developed scoring function, yields very good hit rates for a ligand pool seeded with known actives.

PMID:
12479928
[PubMed - indexed for MEDLINE]
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