On Mon, Jun 06, 2005, Laurence Lavelle wrote:
> By protein motion I mean a folded protein in a constant temperature
> simulation (for example with a distance dependent dielectric, no
> electrostatic cutoffs, no periodic boundaries) and comparing the protein
> dynamics at different temperatures.
With the above conditions (no solvent, distance dependent dielectric) there is
little reason to expect that either the average structure or the dynamics you
see in the simulation will be realistic. If you want to get any reasonable
account of protein dynamics, you need to be looking at MD simulations in
explicit solvent. If you want good results as a function of temperature, you
should take care that the water model you are using is known to produce good
dynamical results vs. temperature for pure water.
...dac
On 06.06.2005, at 23:43, Laurence Lavelle wrote:
In looking at the dynamical motion of a protein, is Amber (Cornell et
al. (1994) force field) (Amber 99 parameters) considered a reasonably
realistic protein force field (or, as good as or better than most) ?
In looking at the dynamical motion of a protein (for example using
Amber), what are the pros and cons to doing Molecular Dynamics vs
Langevin Dynamics vs Monte Carlo ?
It all depends on what dynamical quantities you wish to calculate, and
on which time scales.
If you look at long time scales for a protein that has a single stable
conformation, then you can get good results with very much simpler
models at much lower cost. See
K. Hinsen, A.J. Petrescu, S. Dellerue, M.C. Bellissent-Funel, G.R.
Kneller
Harmonicity in slow protein dynamics
Chem. Phys. 261, 25-37 (2000)
for an example. At the other end of the time scale spectrum, if your
study involves quantum effects, no Molecular Mechanics model will be
good enough.
As for sampling techniques, note that Monte Carlo is not a dynamical
technique at all (it has no time scale), even though in some situations
a time scale can be assigned a posteriori. Langevin and Brownian
dynamics add an implicit source of friction and thermal energy, which
should correspond to some physical feature of the model, i.e. the
explicit modelling should be less detailed.
In this context, it is worth pointing that the major source of friction
in a protein is not the solvent, as is frequently believed, but fast
interactions in the protein itself. See the article quoted above for a
demonstration.
{Some will say it depends on the details (distance dependent
dielectric vs explicit solvent water molecules, no cutoffs vs with
switched or shifted cutoffs, with or without periodic boundary
conditions, etc.). However I am
Again this depends on the time scales. For slow large-scale motions,
you can leave out electrostatics completely, assuming no unfolding of
course, because on such a coarse length scale the charge density is
practically zero. On the other hand, for localized events, a correct
representation of electrostatics is very important.
hoping (in addition to the above two questions) to get a general
sense of how realistic MD, LD and MC are with respect to illustrating
protein motion.
We don't know that much about how realistic simulations of protein
dynamics are. Experimental information is mostly on very small time
scales or on time scales so long that they are out of reach of
simulations. In between those two extremes, there is nothing that
simulations could be tested against.
Konrad Hinsen