Statistical mechanics of proteins : perspective from theory, evolutionary analysis and simulations
Eugene Shakhnovich (Chemistry and Chemical Biology, Harvard University)

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Ces séminaires ont lieu le jeudi à 13h30 en salle de conférence IV au 2ème étage du batiment dit "de chimie".

Jeudi 31 Janvier

In this lecture I will present background and recent developments in
protein theory that provide a unified statistical-mechanical view of
protein folding and evolution. First we will discuss the physical and
statistical requirements for protein sequences to fold cooperatively
into a stable unique conformation - an "energy gap criterion". Next,
based on this criterion we present a mean-field picture of protein
evolution which provides insights on how protein sequences were
discovered in the process of natural selection. These ideas provide
guidance in building models of real proteins which remain tractable by
modern computational methods but which retain most key features of
protein energetics such that native structures retain their key
property of being global energy minima. These energetic schemes are
combined with novel Monte-Carlo simulations of protein folding in
which all heavy atoms are represented as interacting hard spheres of
various sizes corresponding to their van-der-Waals radii. Simulations
of this model result in folding to the native structures with near
X-ray accuracy. By recording many folding events over over a wide
range of temperatures a possible microscopically detailed folding
mechanism for several small proteins obtained, using novel
graph-theoretical analysis to identify robust invariant features of
folding process. Further, using a novel computational approach (Pfold
analysis) we were able to fully characterize Transition State Ensemble
of a number of proteins providing detailed predictions that can be
further tested by experiments. These results present a
"proof-of-principle" for the possibility of a solution of protein
folding problem at an all-atom level, provided that one has a
realistic all-atom potential energy function that correctly favors the
native state.

Ces séminaires ont lieu le jeudi à 13h30 en salle de conférence IV au 2ème étage du batiment dit "de chimie".