title: Conformational proofreading: the impact of conformational changes on the specificity of molecular recognition.
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 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.
authors.affiliation: Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Savir
authors.forename: Tsvi
authors.initials: T
authors.lastname: Tlusty
mesh_terms: D008024:Ligands; D008968:Molecular Conformation
chemical_list: D008024:Ligands