Speaker
Prof.
Jose Onuchic
(Center for Theoretical Biological Physics, University of California at San Diego)
Description
Globally the energy landscape of a folding protein resembles
a partially rough funnel with reduced energetic frustration.
A consequence of minimizing energetic frustration is that
the topology of the native fold also plays a major role in
the folding mechanism. Some folding motifs are easier to
design than others suggesting the possibility that evolution
not only selected sequences with sufficiently small
energetic frustration but also selected more easily
designable native structures. The overall structures of the
on-route and off-route (traps) intermediates for the folding
of more complex proteins are also strongly influenced by
topology.
Going beyond folding, the power of reduced models to study
the physics of protein assembly, protein binding and
recognition, and larger biomolecular machines has also
proven impressive. Since energetic frustration is
sufficiently small, native structure-based models, which
correspond to perfectly unfrustrated energy landscapes, have
shown to be a powerful approach to explore larger proteins
and protein complexes, not only folding but also function
associated to large conformational motions. Therefore a
discussion of how global motions control the mechanistic
processes in the ribosome and molecular motors will be
presented. For example, this conceptual framework is
allowing us to envisage the dynamics of molecular motors
from the structural perspective and it provides the means to
make several quantitative predictions that can be tested by
experiments.
