A molecular mechanics approach to modeling protein-ligand interactions: relative binding affinities in congeneric series.

ABSTRACT: We introduce the "Prime-ligand" method for ranking ligands in congeneric series. The method employs a single scoring function, the OPLS-AA/GBSA molecular mechanics/implicit solvent model, for all stages of sampling and scoring. We evaluate the method using 12 test sets of congeneric series for which experimental binding data is available in the literature, as well as the structure of one member of the series bound to the protein. Ligands are "docked" by superimposing a common stem fragment among the compounds in the series using a crystal complex from the Protein Data Bank and sampling the conformational space of the variable region. Our results show good correlation between our predicted rankings and the experimental data for cases in which binding affinities differ by at least 1 order of

SUBMITTER: Rapp C 

PROVIDER: S-EPMC3183355 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature