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Conformational Proofreading: The Impact of Conformational Changes on the Specificity of Molecular Recognition

2010/07/26 by Yonatan Savir, Tsvi Tlusty · 1 citation
Biochemistry, Genetics and Molecular Biology · Physics and Astronomy · #q-bio.BM #cond-mat.stat-mech #physics.bio-ph

paper · pdf · doi:10.1371/journal.pone.0000468.

published as PLoS ONE. 2007; 2(5): e468 · http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868595/ http://www.weizmann.ac.il/complex/tlusty/papers/PLoSONE2007.pdf

arxiv created 2010/07/26 · arxiv updated 2010/07/27

Abstract

To perform recognition, molecules must locate and specifically bind their targets within a noisy biochemical environment with many look-alikes. Molecular recognition processes, especially the induced-fit mechanism, are known to involve conformational changes. This arises a basic question: does molecular recognition gain any advantage by such conformational changes? By introducing a simple statistical-mechanics approach, we study the effect of conformation and flexibility on the quality of recognition processes. Our model relates specificity to the conformation of the participant molecules and thus suggests a possible answer: Optimal specificity is achieved when the ligand is slightly off target, that is a conformational mismatch between the ligand and its main target improves the selectivity of the process. This indicates that deformations upon binding serve as a conformational proofreading mechanism, which may be selected for via evolution.

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