title: Allostery in protein domains reflects a balance of steric and hydrophobic effects.
abstract: Allosteric conformational change underlies biological function in many proteins. Allostery refers to a conformational event in which one region of a protein undergoes structural rearrangement in response to a stimulus applied to a different region of the same protein. Here, I show for a variety of proteins that a simple, phenomenological model of the dependence of protein conformation on hydrophobic burial energy allows one to compute low-energy conformational fluctuations for a given sequence by using linear programming to find optimized combinations of sequence-specific hydrophobic burial modes that satisfy steric constraints. From these fluctuations one may calculate allosteric couplings between different sites in a protein domain. Although the physical basis of protein structure is complex and multifactorial, a simplified description of conformational energy in terms of the hydrophobic effect alone is sufficient to give a mechanistic explanation for many biologically important allosteric events.
authors: 263 Icahn Laboratory, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. jengland@princeton.edu
authors: Jeremy L
authors: JL
authors: England
mesh_terms: D000465:Algorithms; D000494:Allosteric Regulation; D000495:Allosteric Site; D057927:Hydrophobic and Hydrophilic Interactions; D007536:Isomerism; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D011506:Proteins