The 2013 Nobel prize in Chemistry was a great news for all of us working in the field of computer modeling of biomolecules. M. Karplus, M.Levitt and A. Warshel were recognized for their seminal work on multi-scale modeling of bio-systems, namely for having posed the basis of mixed quantum/classical simulations. However, I like to think the award in a more broad sense, modern science is not anymore solely a duet between experiments and theory. Computation is up there as the third leg of knowledge, a new world with its algorithms, its theory and its in silico experiments. On this regards, I remember a nice discussion by G. Ciccotti on the role of computing in modern theoretical physics, see here.
Back to the topic of this blog, I just wanted to cite three works from the Nobel’s laureates that are especially important when investigating protein thermostability. The first is a work from V.Daggett and M.Levitt (J.Mol.Biol.1993, see here) where the unfolding pathway of a globular protein is explored by performing high-temperature simulations. The second one is from T.Lazaridis, I. Lee and M. Karplus (Protein Sci. 1997, see here) where the stability of the hyperthermophilic protein Rubredoxin from Pyrococcus furiosus is compared to that of the mesophilic homologue and discussed vis-à-vis of protein rigidity and flexibility. The final one is from M. Roca, H.Liu, Messer and A. Warshel (Biochemistry, 2007, see here). Here, the authors tackle the problem of protein function at high temperature, and in particular they challenge the common view according to which the lack of activity of thermophiles at ambient conditions relates to a more rigid behavior of the protein.
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| The first Molecular Dynamics simulation of hard-spheres run on a Univac calculator (BJ Alder and TE Wainwright, JCP, 1957, 27, 1208). For historical curiosity, see the interview to BJ Alder here and an overview by WW Wood on Monte Carlo methods, here. |
