title: Molecular dynamics analysis to evaluate docking pose prediction.
abstract: The accurate prediction of a ligand-protein complex structure is important for computer-assisted drug development. Although many docking methods have been developed over the last three decades, the success of binding structure prediction remains greatly limited. The purpose of this study was to demonstrate the usefulness of molecular dynamics (MD) simulation in assessing a docking pose predicted using a docking program. If the predicted pose is not unstable in an aqueous environment, MD simulation equilibrates the system and removes the ligand from the predicted position. Here we investigated two proteins that are important potential therapeutic targets: β2 adrenergic receptor (β2AR) and PR-Set7. While β2AR is rigid and its ligands are very similar to the template ligand (carazolol), PR-Set7 is very flexible and its ligands vary greatly from the template ligand (histone H4 tail peptide). On an empirical basis, we usually expect that the docking prediction is accurate when the protein is rigid and its ligands are similar to the template ligand. The MD analyses in this study clearly suggested such a tendency. Furthermore, we discuss the possibility that the MD simulation can predict the binding pose of a ligand.
authors.affiliation: Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, the University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Sakano
authors.affiliation: Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, the University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Md Iqbal
authors.initials: MI
authors.lastname: Mahamood
authors.affiliation: Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, the University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, the University of Tokyo, Tokyo 153-8904, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujitani
keywords: G-protein coupled receptor; drug design; histone methyltransferase; ligand–protein complex; molecular dynamics simulation