conformational proofreading the impact of conformational changes on the specificity of molecular recognition构象校对构象变化的影响在分子识别的特异性.pdf

Conformational Proofreading: The Impact of Conformational Changes on the Specificity of Molecular Recognition Yonatan Savir, Tsvi Tlusty* Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel 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 raises 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. Citation: Savir Y, Tlusty T (2007) Conformational Proofreading: The Impact of Conformational Changes on the Specificity of Molecular Recognition. PLoS ONE 2(5): e468. doi:10.1371/journal.pone.0000468 INTRODUCTION detailed kinetic schemes have been suggested and their potential Practically all biological systems rely on the ability of bio-molecules effects on specificity have been discussed – however without direct relation to concrete conformational mechanisms. Here we to specifically recognize each other. Exampl