Science Literature

If proteins and enzymes could not recognise their targets, cellular chemistry would be in chaos. "It was realized early that recognizing molecules should be complementary in shape, akin of matching lock and key". The metaphor of lock and key has served many generations of biology students well - only when the protein key meets the substrate lock do the molecules bind and generate a response. However, "half a century of research has shown, however, that in numerous cases, the molecules need to deform in order to bind, as the key is not an exact fit for the molecular lock." What is to be made of these findings? "Why search for a key that does not match its lock exactly, and then require that the imperfect key warp its shape to fit the lock?" Is this an indication that evolution is a tinkerer and cannot get it right? Is it an example of biology making sense without an intelligent designer?
Actually no. The authors of new study of this phenomenon asked one simple question: "Does molecular recognition gain any advantage by such conformational changes?" They concluded that a definite advantage is present. "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." In more popular language: "The researchers' model shows that the key's deformation actually helps in discerning the right target. Although the energy required to deform the molecular key slightly lowers the probability of its binding to the right target, it also reduces the probability that it will bind to a wrong one by quite a bit."
"This simple mechanism is coined "conformational proofreading" and may explain the observed deformations in many biological recognition systems. Furthermore, conformational proofreading may turn out be a crucial factor affecting the evolution of biological systems, and it may also be useful in the design of artificial molecular recognition systems." The authors write: "Our analysis suggests that conformational changes upon binding may arise as the outcome of an evolutionary selection for enhancing recognition specificity in a noisy environment."
So, something that could have been interpreted as evidence for tinkering evolution is discovered to have advantages after all. Furthermore, it has potential for the design of human systems operating in noisy environments. By invoking "evolutionary selection", the authors suggest an evolutionary context for their work. However, there is no evidence that evolutionary selection was involved, and the link with evolutionary theory is gratuitous. This is another example where the questioning of imperfect design has led to the discovery of exquisite design. The simple question asked by the researchers emerges routinely from the perspective of Intelligent Design.

Conformational Proofreading: The Impact of Conformational Changes on the Specificity of Molecular Recognition
Yonatan Savir, Tsvi Tlusty
PLoS ONE 2(5) 2007: e468. doi:10.1371/journal.pone.0000468

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.

See also:

When Off-target Is Right On, Newswise,26 July 2007.