I study the effect of point mutations on the overall dynamics and local unfolding (helix-to-coil transitions) of a helix by accelerated Molecular Dynamics (aMD) in AMBER14. In the literature I read many times phrases like "this protein is very dynamic" and I never understand the foundations of this asseveration, Now my question is: What descriptor we can use to say that a protein is more "dynamic" than another one...I think in RMSF, principal component analysis... and what else? how can we quantify objectively the dynamics of a protein?
Dear Diego,
besides the analyses that you mentioned, consider also structural cluster analysis: by partitioning the configurations explored by your simulations into clusters roughly of the same "volume", you can have an estimate of the effect of a point mutation, i.e., if it increases the number of clusters explored it means that it makes the protein less rigid, and vice versa. There are several easy-to-use software tools to perform cluster analyses, e.g., in the Gromacs suite of programs. Moreover, in case your peptide features slow interconversions among different metastable conformations, if you collect enough statistics you can exploit cluster analysis also to build a Markov state model that provides you with the kinetic rates of interconversion among the possible conformations.
Bests,
Fabio Pietrucci
Hi Fabio, thank you for your reply. Coincidentally, I'm seeing the analysis routines gromacs and I'm interested in the Markov analysis you mention, can you recommend me some references applied to protein systems? Thank you again!
Regards
Diego, you might want to look here: PLoS ONE, 7(5), e33931. doi:10.1371/journal.pone.0033931.t004
Table 2 gives 34 different descriptors of protein dynamics.
Hi Diego,
I suggest the following articles for clustering + MSM:
J. Shao, S. W. Tanner, N. Thompson, and T. E. Cheatham, J. Chem. Theory Comput.
3, 2312 (2007)
P. Cossio, A. Laio, and F. Pietrucci, Phys. Chem. Chem. Phys. 13, 10421 (2011)
W. C. Swope, J. W. Pitera, and F. Suits, J. Phys. Chem. B 108, 6571 (2004).
N.-V. Buchete and G. Hummer, J. Phys. Chem. B 112, 6057 (2008).
G. R. Bowman, K. A. Beauchamp, G. Boxer, and V. S. Pande, J. Chem. Phys. 131, 124101 (2009).
Hi Ulf and Fabio, I really appreciate your comments, very nice papers. Thank you! Regards!
Diego
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