Work

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

Year: 2007

Type: article

Abstract: 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 the 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 and 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.

Source: Journal of Medicinal Chemistry

DOI: 10.1021/jm070484a

Authors: Bing Wang, Lance M. Westerhoff, Kenneth M. Merz

Institution: University of Florida

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Computational Theory and Mathematics

Field: Computer Science

Domain: Physical Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Awards: G2394479068, Enhancement and Deployment of the Quantum Mechanical NMR Pose Scoring Method