The wrong key

Scientists from the Weizmann Institute discovered how the real biological computer works - the one inside every cell in our body

Right: Yonatan Sabir and Dr. Zvi Telusti. proofreading

In order for them to survive, exist and function, all living things are constantly performing countless complex calculations. Man-made computers are built from stationary components carefully arranged on an electronic chip. But the molecules that make up the biological "computers" move around inside the living cell, and must meet the particular partner that suits them and bind to it, in the thick and random molecular soup that makes up the inside of the cell. The chance of such a chance encounter is similar to the chance of a couple meeting at random in a subway station in Tokyo, during rush hour. And yet, thousands of such encounters take place in the cells and drive the mechanisms of life.

The classic explanation for the ability of biological components to recognize molecular components is based on the concept that the binding molecules fit together like a lock to a key that opens it. However, it has been known for about five decades that in many processes based on such identification, the participating molecules change their shape during binding - that is, the original shape of the key does not exactly match the molecular lock. Why is this change taking place? What is its role in nature?

Research student Yonatan Sabir and Dr. Zvi Telesti from the Department of Physics of Complex Systems at the Weizmann Institute of Science offer a possible answer to this intriguing question. They created a simple biophysical model that shows that in order to identify the correct lock among all similar locks, the key actually "prefers" the lock with which it is not fully matched. Why use a key that does not exactly match the lock? Why complicate molecular identification by requiring a preliminary structural change of the imperfect key to fit the lock?

The model created by Weizmann Institute scientists shows that such a shape change helps distinguish the real target from all the molecules that look like it. It is true that "wasting" the energy on changing the structure of the molecular key somewhat reduces its chances of being attached to a suitable lock, but at the same time it also greatly reduces its chances of being attached to the wrong lock. Thus, it turns out that the final result of this method of operation ensures that the quality of the identification, defined by the ratio between the chances of correct attachment to the chances of incorrect attachment, increases.

The simple mechanism identified by the researchers, which they called "conformational proofreading" may explain the structural changes observed in many systems based on biological recognition. Furthermore, it can be assumed that the formal proofreading affects the evolution of biological systems, and that in the future it will be possible to use it as a central tool for designing artificial biological systems, based on molecular recognition.