Re: [AMBER] free energy of solvation of small molecules

From: Fabian gmail <>
Date: Wed, 2 Dec 2015 16:49:20 +0200

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?



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

> On 2 Dec 2015, at 3:42 PM, Jason Swails <> wrote:
> On Wed, Dec 2, 2015 at 7:41 AM, Fabian gmail <>
> 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
> _______________________________________________
> AMBER mailing list

AMBER mailing list
Received on Wed Dec 02 2015 - 07:00:05 PST
Custom Search