BINDING CONFORMERS SEARCHING METHOD FOR LIGANDS ACCORDING TO THE STRUCTURES OF THEIR RECEPTORS AND ITS APPLICATION TO THROMBIN INHIBITORS

AIM: To develop a method of finding binding conformers for ligands acc ording to the three-dimensional structures of their receptors. METHODS : Combining the systematic search method of ligand with the molecular docking approach of ligand fitting into its receptor, we developed a b inding conformer searching method for ligands. RESULTS: The binding co nformers of phosphonopeptidyl thrombin inhibitors were recognized. The binding (interaction) energies between these inhibitors and thrombin were calculated with molecular mechanical method. CONCLUSION: Both of the total binding energies and steric binding energies have good corre lations with the inhibitory activities of these thrombin inhibitors, d emonstrating that our approach is reasonable. It can also be used to e xplain the inhibition mechanism of thrombin interacting with these inh ibitors.