An NMR-based scoring function improves the accuracy of binding pose predictions by docking by two orders of magnitude.

ABSTRACT: Low-affinity ligands can be efficiently optimized into high-affinity drug leads by structure based drug design when atomic-resolution structural information on the protein/ligand complexes is available. In this work we show that the use of a few, easily obtainable, experimental restraints improves the accuracy of the docking experiments by two orders of magnitude. The experimental data are measured in nuclear magnetic resonance spectra and consist of protein-mediated NOEs between two competitively binding ligands. The methodology can be widely applied as the data are readily obtained for low-affinity ligands in the presence of non-labelled receptor at low concentration. The experimental inter-ligand NOEs are efficiently used to filter and rank complex model structures that have been pre-se

SUBMITTER: Orts J 

PROVIDER: S-EPMC3266494 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature