LAUSR

Accurate modeling of ligand-binding site structures plays a critical role in structure-based virtual screening. However, the structures of ligand-binding site in most predicted protein models are generally of low quality and in need of refinements. In this work, we present a ligand-binding site structure refinement protocol using molecular dynamics simulation with restraints derived from predicted binding site templates. Our benchmark validation shows great performance when tested against 40 diverse set of proteins from the Astex list. The ligand-binding site on modeled protein structures are consistently refined using our method with an average C⍺ RMSD improvement of 0.90 Å. Comparison of ligand binding modes from ligand docking to initial and refined structures shows an average of 1.97 Å RMSD improvements in the refined structures. These results demonstrate a promising new method of structure refinement for protein ligand-binding site structures.