FMO Analysis for Intermoleular Interaction Energy between Human Coagulation Factor Xa and Four Ligands

Abstract

The role of water in the protein-ligand binding site was investigated from the viewpoint of enthalpic bridging between human coagulation factor Xa (fXa) and four ligands. Ligand-constrained MD simulation was done for identifying hydration sites and representative water molecules were arranged at the sites. The calculated fXa-ligand interaction energy while considering these explicit water molecules as parts of fXa shows excellent correlation to the experimental binding affinity, while the energy with considering them as implicit solvent does not correlate. This result indicates that the representative water molecules at the hydration sites should be explicitly considered when protein-ligand interaction energy is analyzed, and ligand-constrained MD simulation is a powerful tool to identify these hydration sites.