Department of Physics and Institute for Brain and Neural Systems Presented:
“Frontiers in the Interaction Between Physics and Biology”
Professor
Seth Fraden (Complex Fluids Group, Brandeis University)
October 6, 2003, 4:00 PM; Barus and Holley, Room 168
"B_2 or Not B_2"
Abstract:
X-ray diffraction of protein crystals is the primary way of deducing protein
structure, which is of importance in elucidating protein function and to the
development of drugs. Crystallization as practiced today is a trial and error
method. About 4,000 of the 30,000 human proteins have been crystallized indicating
the errors have the upper hand. With the completion of the human genome project,
expression of the entire human protein corpus is a possibility. This is viewed
as an important step in the new field of “proteomics.”
Recently it was noticed that all proteins that crystallized had second (osmotic)
virial coefficients (B2) that fell in a small range of values. Frenkel (Science,
97) proposed that this was due to the presence of a metastable critical point
underlying the equilibrium phase diagram. We test this concept by employing
non-absorbing polymers to create a potential of mean force between the proteins
that would influence the position of the critical point. Our experiments and
those of others reveal systematic and general trends that are indicative of
an underlying physical explanation of crystallization in contrast to the “lock
and key” mechanism favored by biochemists. Our experiments demonstrate
that the “depletion” picture is over simplified and that explicitly
including the polymer and protein on equal footing in free energy models is
the correct approach. Theoretical modeling of the phase behavior is needed to
remove crystallization as a bottleneck in determination of protein structure.
