Pose scoring by NMR.

Bing Wang; Kaushik Raha; Kenneth M Merz

doi:10.1021/ja047695e

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Pose scoring by NMR.

Bing Wang·Kaushik Raha·Kenneth M Merz

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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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Binding Sites Ligands Molecular Conformation Nuclear Magnetic Resonance, Biomolecular Pyrrolidines Tacrolimus Binding Protein 1A Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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Bing Wang, Kaushik Raha, Kenneth M Merz. 2004-09-22. Pose scoring by NMR.. https://doi.org/10.1021/ja047695e

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