A three-year PhD studentship at the interface of molecular simulation
and crystallography will be available at the University of Orléans,
starting in October 2009. The research work will be done at the
Synchrotron SOLEIL, 20 km from Paris.
Applicants should have a masters degree in physics or a related field
and should have some experience in working with computers. Please
send applicatons by e-mail, including a CV and a list of referees, to
Konrad Hinsen <hin...@cnrs-orleans.fr>. The deadline for applications
is June 15. For more information about the research group, see its
Web site at http://dirac.cnrs-orleans.fr/.
Thesis subject:
Macromolecular crystallography is well known as a technique for
obtaining the structure of biological macromolecules (proteins, DNA,
RNA) and their complexes. However, it also provides information about
the structural flexibility of these molecules, which remain barely
exploited at the moment. The flexibility is of significant interest
in biology because many biological processes depend on it. For
example, an enzyme has to be flexible in order to adapt itself to the
molecule whose chemical transformation it catalyzes.
In the diffraction images that are obtained when a macromolecular
crystal is exposed to an X-ray beam, one can easily detect deviations
from the theoretical images that would be obtained for a perfect
crystal. These deviations are due partly to crystal defects, but also
to the flexibility of the molecules. Traditionally, macromolecular
crystallography concentrates on obtaining the molecular structure and
eliminates in the course of data processing much of the information
about flexibility and crystal defects. One reason for this is that
the data quality used to be insufficient for a more detailed
description of flexibility. A modern synchrotron light source is
required for obtaining more precise images that permit an analysis of
macromolecular flexibility.
The topic of the proposed thesis is the development of new methods
for the interpretation of crystallographic data with the goal of
separating crystal defects and flexibility and of characterizing the
latter. These techniques will be based on molecular simulation, a
method that is becoming increasingly important in the interpretation
of experimental data. Molecular simulation makes it possible to
describe a macromolecular crystal in more detail than the simpler
models currently used in crystallography, at the price of a higher
computational effort. In the course of the thesis work, the student
will have the opportunity to acquire experience in molecular
simulation, statistical physics, macromolecular crystallography, and
scientific computing.
