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197 Complexity and simplicity of ligand–macromolecule interactions: the energy landscape perspective Gennady M Verkhivker*, Djamal Bouzida, Daniel K Gehlhaar, Paul A Rejto, Stephan T Freer and Peter W Rose The energy landscape approach has contributed to recent the conformational space, and the complex nature of progress in understanding the complexity and simplicity of interactions on the underlying energy landscape [8–12]. ligand–macromolecule interactions. Significant advances in This review discusses recent developments in understanding computational structure prediction of ligand–protein the complexity and simplicity of ligand–macromolecule complexes have been made using approaches that include the interactions by exploiting similarities between protein effects of protein flexibility and incorporate a hierarchy of folding and molecular recognition phenomena derived energy functions. The results suggest that the complexity of from the statistical theory of the energy landscapes. structure prediction in molecular recognition may be determined by low-resolution properties of the underlying Computer simulations of ligand–protein binding, based on binding energy landscapes and by the nature of the energy molecular docking and scoring, have been widely used in funnels near the native structures of the complexes. applications to computational structure prediction of ligand–protein complexes, virtual screening of large data- Addresses bases for active compounds and binding affinity prediction De