title: Ensemble properties of network rigidity reveal allosteric mechanisms.
abstract: The distance constraint model (DCM) is a unique computational modeling paradigm that integrates mechanical and thermodynamic descriptions of macromolecular structure. That is, network rigidity calculations are used to account for nonadditivity within entropy components, thus restoring the utility of free-energy decomposition. The DCM outputs a large number of structural characterizations that collectively allow for quantified stability-flexibility relationships (QSFR) to be identified. In this review, we describe the theoretical underpinnings of the DCM and introduce several common QSFR metrics. Application of the DCM across protein families highlights the sensitivity within the set of protein structure residue-to-residue couplings. Further, we have developed a perturbation method to identify putative allosteric sites, where large changes in QSFR upon rigidification (mimicking ligand-binding) detect sites likely to invoke allosteric changes.
authors: Department of Physics and Optical Science, University of North Carolina at Charlotte, Charlotte, NC, USA. djacobs1@uncc.edu
authors: Donald J
authors: DJ
authors: Jacobs
authors: Dennis R
authors: DR
authors: Livesay
authors: James M
authors: JM
authors: Mottonen
authors: Oleg K
authors: OK
authors: Vorov
authors: Andrei Y
authors: AY
authors: Istomin
authors: Deeptak
authors: D
authors: Verma
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011506:Proteins