CORCEMA evaluation of the potential role of intermolecular transferred NOESY in the characterization of ligand-receptor complexes

Journal of Computer-aided Molecular Design
E V CurtoN R Krishna

Abstract

We report a theoretical characterization of the intermolecular transferred NOESY (inter-TrNOESY) between ligands and receptor macromolecules that bind reversibly, using a COmplete Relaxation and Conformational Exchange MAtrix (CORCEMA) theory developed in our laboratory. We examine the dependence of inter-TrNOESY on the dissociation constant, off-rate, ligand-to-receptor ratio, and distance variations between protons of interacting species within the complex. These factors are analyzed from simulations on two model systems: (i) neuraminidase complexed to a transition-state analogue; and (ii) thermolysin complexed to a leucine-based inhibitor. The latter case utilizes a three-state model of interaction to simulate the effect of hinge-bending motions on the inter-TrNOESY. Our calculations suggest a potential role for inter-TrNOESY (when observable) and CORCEMA analysis in properly docking the ligand within the active site, and in refining the conformation of the ligand-receptor (active-site) complex. These findings have implications on the structure-based design of ligands (e.g., inhibitors) reversibly binding to receptors (e.g., enzymes).

References

Jan 1, 1989·Methods in Enzymology·D M LeMaster
Jan 1, 1989·Methods in Enzymology·B A Borgias, T L James
May 31, 1972·Journal of the American Chemical Society·R NoyoriH Takaya
Nov 1, 1980·Biopolymers·N R KrishnaJ D Glickson
Jun 1, 1994·Biophysical Journal·M RadmacherP K Hansma
Sep 1, 1993·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J AnglisterD Feigelson

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Citations

Feb 19, 2014·Progress in Nuclear Magnetic Resonance Spectroscopy·Beat Vögeli
Jul 14, 2006·European Journal of Medicinal Chemistry·C BonechiC Rossi
Aug 1, 2015·Journal of Chemical Information and Modeling·Ionut OnilaThomas E Exner
Oct 14, 2008·Chembiochem : a European Journal of Chemical Biology·Anirban BhuniaBeat Ernst
Jan 16, 2003·Molecular Pharmacology·Birgit L CoffmanThomas R Tephly
Mar 28, 2008·Journal of Medicinal Chemistry·Marina CioffiAndrea Spitaleri

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