Re: [AMBER] restraint 10 kcal/mol

From: Debarati DasGupta <>
Date: Thu, 25 Jun 2020 13:12:18 +0000

Hello Prof Case,
Thank you for clearing out the restraint_mask functionality.
SO does that mean, in the bigger picture, whatever I did to set up my absolute binding free energy calculations is totally wrong?
Using a co-solvent based approach, I have certain x,y,z locations of a set small molecules (ethanol, isopropanol, acetonitrile, phenol, pyridine etc) and I am interested to compute the absolute free energy of binding (using TI) of these small probes to my kinase.
All I know is locations ( in terms of x y z coordinates) where the probe density is maximum, that is, places on the protein where the probe sticks to it.
So, given that information, how to modify my input files so that I can set up TI calculations to compute free energies of binding.
I wanted to mention these are small molecules ( all < 15 atoms) and are weak binders, so the range I am looking at is -1 to -3 kcal/mol roughly..
So in your opinion how should I set up the restraint..?


From: David A Case<>
Sent: 24 June 2020 21:36
To: Debarati DasGupta<>
Subject: Re: restraint 10 kcal/mol

On Wed, Jun 24, 2020, Debarati DasGupta wrote:

> ntr=1, restraintmask=':EOH', restraint_wt=10.00,

Note this will keep the EOH residue from moving, but all other parts of
the simulation are free to go where they wish. This doesn't keep the
ligand "in the pocket"; it just keeps the xyz coordinates of the EOH
atoms near their starting point. Basically, all this will do is to
ensure that internal geometry of EOH is kept fixed. I doubt that is
really what you wanted to do: since ethanol is rather rigid anyway, this
is almost like having no restraint at all.

>So, after the run was complete, I was curious to see how far my ligand
>has translated from its tether point.. and after doing a COM distance
>cpptraj script run, I find that for 3 lambda values 0.11505, 0.20634,
>and 0.31608; the ligand has moved around quite a bit as in > 3 Angstroms

It's not at all clear what you mean by a "COM distance cpptraj script";
but I hope the explanation of the restraint mask above will help.


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Received on Thu Jun 25 2020 - 06:30:04 PDT
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