Open AccessConformational Proofreading: The Impact of Conformational Changes on the Specificity of Molecular Recognition
Author(s) -
Yonatan Savir,
Tsvi Tlusty
Publication year - 2007
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0000468
Subject(s) - proofreading , molecular recognition , conformational change , chemistry , mechanism (biology) , flexibility (engineering) , biophysics , conformational ensembles , ligand (biochemistry) , computational biology , molecule , protein structure , computer science , stereochemistry , biochemistry , biology , physics , dna , mathematics , statistics , receptor , organic chemistry , quantum mechanics , polymerase
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.