  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.
