Harmonic analysis and approximations made by NMA break down for proteins at physiological conditions. Since this is an important limitation, can NMA be used to study protein dynamics and make accurate inferences relating to physiological conditions?
Hallo,
we are combining neutron spin-echo spectroscopy experiments with NMA calculated from elastic network models. Functionally relevant motions in the time scale of around 50 nanoseconds were studied by my colleagues for the protein phosphoglycerat kinase (PGK) under physiological conditions see Inoue et al. Biophysical Journal 2010, pages 2309 - 2317.
What came out is that the first non-trivial normal modes describe the directions of the measured domain motions quite well, but the amplitudes of the modes need to be fitted to agree with the experimental data.
In a second paper (Smolin et al. Biophysical Journal 2012, pages 1108 - 1117) principal components were calculated from full atomistic MD simulations of PGK. Again, the amplitudes of motion were too small and do not match the experimental results. The directions of the collective motions, however, agreed quite well with the normal modes from the first article.
I hope my answer is helpful,
Andreas
But does it mean that NMA or even ENM data is more reliable than full atomistic MD in simulating protein dynamics physiological-like conditions? Because as you mentioned, in your second paper MD results did not match experimental results but agreed with NMA data
Hallo,
the directions of the principal components from the MD simulations agreed both with the normal modes and with the measured data.
The amplitudes of these motional patters determined from the MD did not agree with experimental data directly (they were by a scaling factor of something to small), but neither did the amplitudes of motion from NMA agree directly with the experimental data.
My point here is just that you can probably simulate the directions of motion under physiological conditions quite realistically by NMA and by ENM (as it is also the case by MD). One should consider the amplitudes of these motions in absolute units and the relaxation rates carefully as they can differ from reality.
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