title: Generation of a flexible loop structural ensemble and its application to induced-fit structural changes following ligand binding.
abstract: Molecular recognition is often mediated by flexible loops that have widely fluctuating structures and are sometimes disordered, but that form particular complex structures following ligand binding. In fact, many loop structures found in the PDB database are too flexible to be determined precisely. A new loop modeling method was therefore developed using force-biased multicanonical molecular dynamics with the implicit solvent model to generate an ensemble of putative loop structures with low free energy values. The method was then used to create ensembles for several flexible loops that were compared with the corresponding NMR and X-ray structures. The induced-fit structural change of dihydrofolate reductase (DHFR) was also predicted from a structural ensemble of ligand-free M20 loop conformations and successive docking simulations.
authors.affiliation: Japan Biological Information Research Center (JBIRC), Japan Biological Informatics Consortium (JBiC), 2-41-6 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Yukihisa S
authors.initials: YS
authors.lastname: Watanabe
authors.affiliation: Biological Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), 2-41-6 Aomi, Koto-ku, Tokyo 135-0064, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Fukunishi
authors.affiliation: Biological Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), 2-41-6 Aomi, Koto-ku, Tokyo 135-0064, Japan; Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Nakamura
keywords: docking simulation; flexible loop modeling; force-biased multicanonical molecular dynamics; induced-fit; structural ensemble