Physicists at the Università di
Firenze, in Italy, have put a new slant on the protein folding
problem. Proteins are special polymers made of amino acids. Generic
polymers, when you cool them enough, will collapse in a ball.
something more interesting: they fold up into a particular compact
form. If a protein fails to find this form it won't be able to carry
out its designated function and disease can result. For instance,
some nonfolding proteins will aggregate into long filaments, amyloid
fibrils, and this has proven to be the basis for neurodegenerative
diseases like Alzheimer's.
Finding the precise dynamics behind protein folding would be like
Isaac Newton finding the laws of universal gravitation. We aren't
at that point yet, but there are ways of investigating some of the
steps proteins take to arrive at their proper form. One fruitful
approach is to see the multi-step process as taking place in a
series of energy transactions. At any moment the protein can be
represented as a point moving around in an abstract space whose
coordinates correspond to all possible configurations and the
associated energy needed to have that structure, sort of like a ball
rolling along on the inner surface of a bowl. The bowl might have
some partitions, and the ball might be able to roll up out of one
compartment and into a neighboring one if its energy is sufficient,
or if the wall between compartments is low enough, or if some extra
energy (maybe in the form of heat or a chemical reaction) is added.
Lapo Casetti (firstname.lastname@example.org) and Lorenzo Mazzoni have attempted
to make the "energy landscape" method even more geometrical by
characterizing the folding forces at work as being a form of
curvature in the bowl-like well in which the protein is operating.
This is analogous to what Albert Einstein did in characterizing
gravity as the curvature of spacetime in which planets and stars
move about. Mazzoni and Casetti seek to determine what it is about
the curvature of the energy landscape that encourages proteins to
fold and other polymers not to fold.
Mazzoni and Casetti,
Physical Review Letters, 24 November 2006
Contact Lapo Casetti
Università di Firenze