A Critical Assessment of the Performance of Protein−Ligand Scoring Functions Based on NMR Chemical Shift Perturbations

Bing Wang, Lance M. Westerhoff, Kenneth M. Merz
2007 Journal of Medicinal Chemistry  
We have generated docking poses for the FKBP-GPI complex using eight docking programs, and compared their scoring functions with scoring based on NMR chemical shift perturbations (NMRScore). Because the chemical shift perturbation (CSP) is exquisitely sensitive on the orientation of ligand inside the binding pocket, NMRScore offers an accurate and straightforward approach to score different poses. All scoring functions were inspected by their abilities to highly rank the native-like structures
more » ... nd separate them from decoy poses generated for a protein-ligand complex. The overall performance of NMRScore is much better than that of energy-based scoring functions associated with docking programs in both aspects. In summary, we find that the combination of docking programs with NMRScore results in an approach that can robustly determine the binding site structure for a protein-ligand complex, thereby, providing a new tool facilitating the structure-based drug discovery process.
doi:10.1021/jm070484a pmid:17867664 pmcid:PMC2525740 fatcat:6cebshczbjcs7kpfzlqo35fcsu