Allosteric Coupling and Conformational Fluctuations in Proteins

Author(s): H. Ongun Onaran, Tommaso Costa

Journal Name: Current Protein & Peptide Science

Volume 10 , Issue 2 , 2009

Become EABM
Become Reviewer
Call for Editor


Proteins in their native folded states can possess multiple energy minima and they can show constant conformational fluctuations at physiological temperatures. In this article, we discuss the quantitative relationship between ligandinduced perturbation of such fluctuations, modeled as probability distributions of conformational substates, and allosteric coupling of ligand binding to different sites, as defined by linkage thermodynamics. We show that allosteric coupling between two binding events on the same protein is an inevitable consequence of ligand-induced perturbations of the probability distribution that represents conformational fluctuations in thermal equilibrium. When high resolution structural data of a protein in empty and ligand-bound forms are available, the COREX algorithm can provide, in principle, an excellent bridge between the energetics of substates distribution in the protein ensemble and structural coordinates. Here we propose a COREX-based strategic approach to link structural perturbations and the free energy changes of allosteric coupling. This strategy might be broadly useful in the endeavor of predicting how specific ligands allosterically regulate the function of specific proteins.

Keywords: Allosteric coupling, native ensemble, COREX algorithm, conformational fluctuation, protein substates, protein function

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2009
Page: [110 - 115]
Pages: 6
DOI: 10.2174/138920309787847644
Price: $65

Article Metrics

PDF: 7