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26.07.2007
Unlike man-made computer components that are
meticulously ordered on a chip, the molecules that make
up biological 'computers' are diffuse within the cell.
All organisms perform intricate molecular computations to survive. Unlike man-made computer
components that are meticulously ordered on a chip, the molecules that make up biological
'computers' are diffuse within the cell. Yet these must pinpoint and then bind to specific
counterparts while swimming in the cell’s thick, erratic molecular stew – something like finding a
friend in a Tokyo subway station during rush hour.
In the classical view of molecular recognition, the binding molecules fit each other like a lock and
key. 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. Why would
evolution choose such an inexact system?
The work of and Dr. Tsvi Tlusty and research student Yonatan Savir of the Weizmann Institute’s
Physics of Complex Systems Department suggests a possible answer. A simple biophysical
model they developed indicates that in picking out the target molecule from a crowd of lookalikes, the recognizer has an advantage if it’s slightly off-target. This may appear to be
counterintuitive: 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?
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. Thus, the quality of recognition – i.e. the ratio of the right to wrong binding
probabilities – increases.
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 bio-logical systems, and it may also be
useful in the design of artificial molecular recognition systems.
Dr. Tsvi Tlusty’s research is supported by the Clore Center for Biological Physics; the Asher and
Jeannette Alhadeff Research Award; and the Philip M. Klutznick Fund for Research.
The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking
multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and
exact sciences, the Institute is home to 2,600 scientists, students, technicians and supporting
staff. Institute research efforts include the search for new ways of fighting disease and hunger,
examining leading questions in mathematics and computer science, probing the physics of
matter and the universe, creating novel materials and developing new strategies for protecting
the environment.
Weizmann Institute news releases are posted on the World Wide Web at http://wiswander.weizmann.ac.il/, and are also available at http://www.eurekalert.org/.