Ph.D., Ecole Normale Superieure and Univ. Paris (2011)
B.Sc., Ecole Normale Superieure and Univ. Paris (2006)
My research in the Berne group mainly deals with various aspects of protein behavior undor force, in strong collaboration with the experimental group of Prof. Julio Fernandez in the biology department. Single molelecule force-spectroscopy techniques are a whole new and exciting field providing unprecedented details about biochemical and biological mechanisms at a molecular scale. However, interpretation of the experimental data is often challenging and benefits from the perspective brought by steered molecular dynamics simulations.
In particular, we have shown that while proteins under force in the experiments sample the same PMF as in the simulations, motions on the free-energy surface are soleley limited by the drag on the objects they are necessarily tethered to. Motions of "free" proteins as studied in simulations or in other experimental techniques (e.g. FRET) are occuring on a much faster timescale; force does not dramatically affect internal diffusion of the protein, only its PMF. These results are of crucial importance for interpretation of experimental rates and free-energy barriers, as well as for biological systems where proteins under tension are often tether to larger macromolecular objects.
On another perspective, we are refining and trying to offer a molecular picture of classic descriptions of proteins under force, such as the worm-like chain model from polymer physics. We address questions such as: what are the protein degrees of freedom affected by force? What is responsible for the protein flexibility? What is the persistence length due to?
Other ongoing projects include the stability of glutathionated proteins or the complex dependence of disulfide reduxion by thioredoxins under force.
On a different perspective, I am also investigating the effect of a small chemical chaperone (trimethylamine N-oxide) both on model and on real protein systems. Together with J. Mondal from the group, we are currently trying to explain the increase in the folding propensity of a small hydrophobic polymer in the presence of TMAO. We contrast it with the action of urea which has been characterized in the group before. We also hope to understand how TMAO influences the folding pathways and kinetics of fast-folding proteins, as well as intrisically disordered protein, as it has been suggested experimentally.
A complete list can be found on my website.
R. Berkovich, R. I. Hermans, I. Popa, G. Stirnemann, S. Garcia-Manyes, B. J. Berne and J. M. Fernandez. Rate Limit of Protein Elastic Response is Tether Dependent, Proc. Natl. Acad. Sci. USA 109, 14416-21 (2012)
G. Stirnemann and D. Laage. Communication: On the Origin of the Non-Arrhenius Behavior in Water Reorientation Dynamics, J. Chem. Phys. 137, 031101 (2012)
F. Sterpone, G. Stirnemann and D. Laage. Communication: Magnitude and Molecular Origin of Water Slowdown Next to a Protein, J. Am. Chem. Soc. 134, 4116-9 (2012)
G. Stirnemann and D. Laage. Direct Evidence of Angular Jumps During Water Reorientation Through Two-Dimensional Infrared Anisotropy, J. Phys. Chem. Lett. 1, 1511-5 (2010)
G. Stirnemann, J. T. Hynes and D. Laage. Water Hydrogen Bond Dynamics in Aqueous Solutions of Amphiphiles, J. Phys. Chem. B 114, 3052-9 (2010)
D. Laage, G. Stirnemann and J. T. Hynes. Why Water Reorientation Slows without Iceberg Formation around Hydrophobic Solutes, J. Phys. Chem. B 113, 2428-35 (2009)