COMPUTATIONAL APPROACHES TO MODELING RECEPTOR FLEXIBILITY UPON LIGAND BINDING: APPLICATION TO INTERFACIALLY ACTIVATED ENZYMES

R. C. WADE¹, V. SOBOLEV², A. R. ORTIZ¹ AND G. PETERS³

¹ European Molecular Biology Laboratory, Meyerhofstr 1,69012 Heidelberg, Germany
² Department of Plant Genetics, Weizmann Institute of Science, Rehovot 76100, Israel
³ Chemistry Department, University of Copenhagen, 2100
Copenhagen and Novo Nordisk, 2880 Bagsvaerd, Denmark

Abstract

Receptors generally undergo conformational change upon ligand binding. We describe how fairly simple techniques may be used in docking and design studies to account for some of the changes in the conformations of proteins on ligand binding. Simulations of protein-ligand interactions that give a more complete description of the dynamics important for ligand binding are then discussed. These methods are illustrated for phospholipase A2 and lipase, enzymes that both undergo interfacial activation.

in "Experimental and Computational Approaches in Structure Based Drug Design"
Ed. P. W. Codding, NATO ASI Series, Kluwer, Dortrecht (1998) 223-232.