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.
An NMR-based scoring function improves the accuracy of binding pose predictions by docking by two orders of magnitude
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...
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[NMR paper] Histogram-based scoring schemes for protein NMR resonance assignment.
Histogram-based scoring schemes for protein NMR resonance assignment.
Related Articles Histogram-based scoring schemes for protein NMR resonance assignment.
J Bioinform Comput Biol. 2004 Dec;2(4):747-64
Authors: Wan X, Tegos T, Lin G
In NMR protein structure determination, after the resonance peaks have been identified and chemical shifts from peaks across multiple spectra have been grouped into spin systems, associating these spin systems to their host residues is the key toward the success of structural information extraction and thus the...
Pose scoring by NMR.
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