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Communication

Pose Scoring by NMR

Bing Wang, Kaushik Raha, and Kenneth M. Merz, Jr.*

152 Davey Laboratory, Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802

J. Am. Chem. Soc., 2004, 126 (37), pp 11430–11431

DOI: 10.1021/ja047695e

Publication Date (Web): August 25, 2004

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, merz@psu.edu

Abstract

Recently, we have developed a fast approach to calculate NMR chemical shifts using the divide and conquer method at the semiempirical level. To demonstrate the utility of this approach for characterizing protein−ligand interactions, we used the deviation of calculated chemical shift perturbations from experiment to determine the orientation of a ligand (GPI-1046) in the binding pocket of the FK506 binding protein (FKBP12). Moreover, we were able to select the native state of the ligand from a collection of decoy poses. A key hydrogen bond between O1 and HN in Ile56 was also identified. Our results suggest that ligand-induced chemical shift perturbations can be used to refine protein/ligand structures.

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