A novel shape-feature based approach to virtual library screening.
The shape of and the chemical features of a ligand are both critical for biological activity. This paper presents a strategy that uses these descriptors to build a computational model for virtual screening of bioactive compounds. Molecules are represented in a binary shape-feature descriptor space as bit-strings, and their relative activities are used to identify the subset of the bit-string that is most relevant to bioactivity. This subset is used to score virtual libraries. We describe the computational details of the method and present an example validation experiment on thrombin inhibitors.
Putta
Santosh
S
Deltagen Research Labs, 740 Bay Road, Redwood City, California 94063-2469, USA. sputta@combichem.com
Lemmen
Christian
C
Beroza
Paul
P
Greene
Jonathan
J
D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical / Q000706:statistics & numerical data*; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D014584:User-Computer Interface
D008024:Ligands