Dear Jason,
Thanks a lot for the detailed explanation, so in the paper I am following, they minimised once, and then use the same minimised molecule (in this case a drug Improving the Efficiency of Free Energy Calculations in the Amber
Molecular Dynamics Package Joseph W. Kaus,*,† Levi T. Pierce,†,‡ Ross C. Walker,†,‡ and J. Andrew cCammon†,§,∥,⊥) and then perform IT calculation.
So the protocol I will be using will something like this:
0) minimize 20,000 steps ONCE for lambda = 0. 5 and then for each lambda
for lambda 0, 0,1, 0,2, etc. … 1 do the following:
1) heating to 300 K during 500 ps at constant pressure
2) equilibrate at constant volume during 500 ps
3) production for 5 ns at constant volume x 3
This protocol is different than in the A9 tutorial, but sounds more right for my purpose, does it sounds a right protocol? This is to calculate the DG of solvation (disspereance of a drug in water).
Additionally, I saw there are man tools to analyze the final DG, what is easiest / best to use?
Thanks!!
Fabian
Dr. Fabian Glaser
Head of the Structural Bioinformatics section
Bioinformatics Knowledge Unit - BKU
The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering
Technion - Israel Institute of Technology, Haifa 32000, ISRAEL
fglaser at technion dot ac dot il
Tel: +972 4 8293701
http://bku.technion.ac.il
> On 2 Dec 2015, at 3:42 PM, Jason Swails <jason.swails.gmail.com> wrote:
>
> On Wed, Dec 2, 2015 at 7:41 AM, Fabian gmail <fabian.glaser.gmail.com>
> wrote:
>
>> Dear Hannes,
>>
>> I bother you again….
>>
>> According to the Kaus paper, it’s clear that only one minimization of the
>> ligand it’s necessary to calculate the solvation free energy, but it’s not
>> clear to me if each lambda value requires a heating and pressure
>> equilibration, and then production, or only one initial heating + equil is
>> necessary and then production continues from the last .rst7 file…. of the
>> last lambda (as in a regular long MD).
>>
>
> In principle, you will always need to do an equilibration. You cannot
> assume that the phase space of different lambda values are the same (in
> fact, they are NOT the same), which means that a snapshot from one lambda
> value will not be an equilibrium structure for another lambda value in
> general. So you will need to perform some amount of MD in order to relax
> the structure to its "new" lambda value and throw out the non-equilibrium
> structures generated on the way to the actual free energy surface.
>
> The more similar these lambda surfaces are (which you can usually guarantee
> by taking small increments of lambda), the less re-equilibration time will
> be needed. The surface similarity can be a lot worse if all you want to do
> is avoid reminimizing and reheating (which means that even if you have to
> re-do the equilibration when moving to an adjacent lambda value, you can
> usually re-use the minimization/heating results from the previous step).
>
> That said, heating and minimization are the cheapest parts of the
> simulation (by far). So there's not really much harm in just redoing it if
> you were concerned about it.
>
> HTH,
> Jason
>
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
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Received on Wed Dec 02 2015 - 07:00:05 PST
