Proteins in Action

Promotion on 29 may 2008

"Proteins in Action, simulations of conformational changes in small proteins" is the title of the PhD thesis that Jaroslaw (Jarek) Juraszek will defend on Thursday, May 29. Jarek investigated, under guidance of his promotor, Peter Bolhuis, folding and unfolding of small proteins by computer simulation. He wrote the following summary of his work on the back of his thesis:

Even though at least trillions of proteins have just folded in the time it takes you to read this sentence, from the physical point of view protein folding is a "rare event". This is because the kinetics of molecules such as proteins should be considered on the appropriate timescale, namely the timescale of the vibrations of atoms. From this perspective, folding takes an enormous amount of atomic vibrations, and this makes the molecular simulations of the process extremely difficult.

This thesis is concerned with addressing the daunting task of simulating the folding of proteins on a molecular level. We discuss algorithms for improving the efficiency of rare event sampling. With these techniques we can predict the folding mechanism on the atomic level, calculate the rate constants and the corresponding transition states. By using simulations, we can as well understand the reasons of misfolding of proteins, which when happening in living organisms may be a source of disease.

We apply the simulation methods to simple polypeptides and small proteins forming both beta-hairpins and alpha-helices, to understand the folding mechanism of subunits of proteins. We finally show that we can go beyond folding simple secondary structures, and that the sampling of large scale conformational changes of biologically-relevant, functional proteins starts to be within our reach.

PhD promotion of
Jaroslaw Juraszek
Prof. Dr. P. G. Bolhuis
Thursday, 29 May 2008, 10 AM
Agnietenkapel of the University of Amsterdam
Oudezijds Voorburgwal 231, Amsterdam