Dynamics of proteins at the nanoscale
CIC nanoGUNE Seminars
- Speaker
-
David de Sancho, University of Cambridge, Cambridge, UK
- When
-
2014/09/29
13:00 - Place
- nanoGUNE seminar room, Tolosa Hiribidea 76, Donostia - San Sebastian
- Add to calendar
-
iCal
**Host** : R. Perez-Jimenez
Atomistic molecular dynamics (MD) simulations provide a uniquely detailed tool
for understanding the dynamics of proteins, the workhorses of living
organisms. Analyzing the results from these simulations is however an
overwhelming task, as it involves making sense of many gigabytes of data
consisting of coordinates of the many degrees of freedom of both the protein
and the surrounding solvent. Markov state models have recently emerged as an
analysis methodology for MD simulations that is able to provide information of
the slow, and usually most relevant, transitions of the system (e.g. folding),
but without loosing the resolution on the microscopic dynamics. One of their
advantages is their fine-grained resolution, which allows for exquisite
comparison of the simulation results with experiment.
I will introduce this approach using a very small peptide as example1.
Studying this system we have been able to calculate the rate of the most
fundamental process in protein folding, helix nucleation, and understand the
origin of the experimental fluorescent signal. Then we will gradually move up
in complexity to show how these models can help us to setup the simulations
for maximum efficiency in rate calculations2 and to solve fundamental
questions in protein folding, in particular the origin of the unusual
viscosity dependence observed experimentally3. Finally I will present
applications of this type of approach to protein engineering in systems of
industrial interest4,5.
1. D De Sancho & R B Best, What is the time scale for α-helix nucleation? _J Am Chem Soc_ **133** , 6809-6816 (2011).
2. D De Sancho, J Mittal & R B Best, Folding kinetics and unfolded state dynamics of the GB1 hairpin from molecular simulations. _J Chem Theory Comput_ **9** , 1743-1753 (2013).
3. D De Sancho*, A Sirur & R B Best, Molecular origin of "internal friction" effects in protein folding rates. _Nat Commun_ **5** , 4307 (2014).
4. A. Kubas, D. De Sancho, R. B. Best & J. Blumberger, Aerobic damage of [FeFe] hydrogenases: activation barriers for O2 chemical attachment. _Angew Chem Int Ed_ **53** , 4081-4084 (2014).
5. D De Sancho, A Kubas, J Blumberger & R B Best, Identification of hot-spots for mutation for substrate diffusion in proteins ( _Submitted_ ).