On Fri, 2015-02-06 at 18:33 +0530, Ruchika Bhat wrote:
> Hello All,
> *(all these are done in solvated medium i.e no vacuum condition)*
> I have two systems
> i) modeled protein and
> ii) one protein-drug complex
>
> I want to use the amber dynamics simulation studies to do analysis of
> protein to check if the modeled structure/conformation is correct or not
> and to check if drug is bound to the protein after running the simulations
> for 10ns or long.
>
> Please suggest me if :
> 1. I should use the same minimization, heating and production for both the
> systems.
I would.
> 2. Is it necessary to include equilibration step after heating, if so why?
Usually. tleap usually builds solvation boxes that are too large, so it
often takes a decent amount of simulation to stabilize the density to
the correct value.
What people typically mean by "equilibration" is a portion of the
simulation that is discarded from analysis because it is used to bring
the system closer to equilibrium. Most systems (except perhaps very
small "toy" systems) will start out with some non-equilibrium property
that needs to be relaxed (perhaps crystal contacts that are unphysical
in solution, refinement/resolution issues, abnormally low solution
density). Including these configurations in your ensemble will bias
that ensemble in an unpredictable (and not easily correctable) way.
> 3. Also I have analyzed the mdcrd file of production till 2ns, it is
> showing the pressure varying but I have used the NTP ensemble production
> input file . What could be the possible reason for it?
NTP means you are holding the *external* pressure constant. The
pressure reported by sander is the internal pressure, which will
fluctuate naturally as the system volume responds instantaneously to the
external pressure. The average internal pressure will equal the
external pressure, but instantaneously it will fluctuate. The
fluctuations in typical biomolecular simulations is so huge (often +-100
to 1000 bar) because the isothermal compressibility of liquids
(particularly water) is so small.
That is, huge pressure changes gives rise to relatively small volume
changes (barring a phase change, of course). Or in the case of sander,
the inverse (i.e., small changes in volume gives rise to the huge
pressure fluctuations you see).
> 4. Is it always advisable to heat the solvent first and then slowly heating
> up the protein? or we can heat the solvated protein simultaneously along
> with the solvent at the start without restraints.
It is unclear whether you mean the solvent and solute should be hooked
to separate temperature baths (unusual in my experience, and not
something Amber really supports), or if you meant that the solute is
restrained while the system is heated.
In the latter, the solute is *still* heated -- it just doesn't move very
far from its original position. Whether this is necessary probably
depends on your system. I usually restrain the backbone atoms (only)
with weak-ish (ca. 0.5 to 1 kcal/mol/A^2) restraints and heat the system
up uniformly, but quickly (over ~100 ps or so) at NVT. Then I switch to
NPT to equilibrate the density (the short heating prevents the formation
of vacuum bubbles, which can be hard to press out after they form). For
highly flexible systems that can be very sensitive to small changes in
the solvent distributions (like nucleic acids), I restrain the backbone
through this whole process. For more rigid systems (like many
proteins), I might not.
HTH,
Jason
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
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Received on Fri Feb 06 2015 - 07:00:02 PST
