Enrichment of chemical libraries docked to protein conformational ensembles and application to aldehyde dehydrogenase 2.

ABSTRACT: Molecular recognition is a complex process that involves a large ensemble of structures of the receptor and ligand. Yet, most structure-based virtual screening is carried out on a single structure typically from X-ray crystallography. Explicit-solvent molecular dynamics (MD) simulations offer an opportunity to sample multiple conformational states of a protein. Here we evaluate our recently developed scoring method SVMSP in its ability to enrich chemical libraries docked to MD structures of seven proteins from the Directory of Useful Decoys (DUD). SVMSP is a target-specific rescoring method that combines machine learning with statistical potentials. We find that enrichment power as measured by the area under the ROC curve (ROC-AUC) is not affected by increasing the number of MD structures.

SUBMITTER: Wang B 

PROVIDER: S-EPMC4114474 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature