title: Rigidity Theory-Based Approximation of Vibrational Entropy Changes upon Binding to Biomolecules.
abstract: We introduce a computationally efficient approximation of vibrational entropy changes (ΔSvib) upon binding to biomolecules based on rigidity theory. From constraint network representations of the binding partners, ΔSvibis estimated from changes in the number of low frequency ("spongy") modes with respect to changes in the networks' coordination number. Compared to ΔSvibcomputed by normal-mode analysis (NMA), our approach yields significant and good to fair correlations for data sets of protein-protein and protein-ligand complexes. Our approach could be a valuable alternative to NMA-based ΔSvibcomputation in end-point (free) energy methods.
authors.affiliation: Institute for Pharmaceutical and Medicinal Chemistry, Department of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf , 40225 Düsseldorf, Germany.
authors.forename: Holger
authors.identifier: http://orcid.org/0000-0001-8613-1447
authors.initials: H
authors.lastname: Gohlke
authors.affiliation: Institute for Pharmaceutical and Medicinal Chemistry, Department of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf , 40225 Düsseldorf, Germany.
authors.forename: Ido Y
authors.initials: IY
authors.lastname: Ben-Shalom
authors.affiliation: Institute for Pharmaceutical and Medicinal Chemistry, Department of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf , 40225 Düsseldorf, Germany.
authors.forename: Hannes
authors.initials: H
authors.lastname: Kopitz
authors.affiliation: R&D/Pre-Development Sciences, Sanofi-Aventis Deutschland GmbH , Industriepark Höchst, 65926 Frankfurt am Main, Germany.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pfeiffer-Marek
authors.affiliation: R&D Resources/Site Direction, Sanofi-Aventis Deutschland GmbH , Industriepark Höchst, 65926 Frankfurt am Main, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Baringhaus
mesh_terms: D001665:Binding Sites; D019277:Entropy; D011506:Proteins / Q000737:chemistry*; D011789:Quantum Theory; D054852:Small Molecule Libraries / Q000737:chemistry*; D014732:Vibration
chemical_list: D011506:Proteins; D054852:Small Molecule Libraries