Binding Energy Landscapes of Ligand-Protein Complexes and Molecular Docking: Principles, Methods, and Validation Experiments

Deciphering of the common successes and failures in ligand-protein docking, revealed by using different docking strategies and energy functions, allows one to establish fundamental connections between the topology of binding energy landscapes and the results of docking simulations. Binding energy landscape analysis is presented for the methotrexate-dihydrofolate reductase system, which represents a common success in molecular docking of ligand-protein complexes, and for the cyclodextrin glycosyltransferase-maltose complex, which is an example of a common failure in molecular docking simulations. The successes and failures in docking simulations are explained based on the ther-

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