Computational conformational analysis of alpha-thrombin inhibitors possessing distinct scaffolds in aqueous solution and on Ala-sheet

摘要

Recent computational simulations on protein-ligand binding/unbinding have precisely been uncovering the ligand-binding process at the atomic level. In the process, the non-specific binding of ligands to the target site is suggested to occur before binding to the target. We in this study analyzed the conformations of ligands under the non-specific binding on a protein surface to figure out the differences in the conformational characteristics in aqueous solution using the 55-ns molecular dynamic simulation. As for the protein surface, we constructed an artificial beta-sheet, composed of poly-alanine residues (Ala-sheet). For the ligands, the four alpha-thrombin inhibitors possessing two scaffolds with distinct hydrophobicity profiles were used.