Hi,
What you are trying do is a relative free energy simulation. Your softcore masks are identical with the TI region which means that you are running purely dual-topology, i.e. you have two independent copies. No wonder that they drift apart.
What you probably should do is to find a suitable mapping between two ligands. Programs like FEW (part of the AmberTools) or FESetup can help you doing this. The mapped region would than be treated via a single topology which implies also a single coordinate set for those atoms. This provides you with a suitable "anchor" which a) ties your ligands together and b) does not have completely vanishing end states similar as you would have in an absolute free energy simulation (you could consider a simulation as you have attempted to be two absolute calculation simultaneously but only getting half of the results).
Cheers,
Hannes.
________________________________________
From: vladimir.palivec.marge.uochb.cas.cz [vladimir.palivec.marge.uochb.cas.cz]
Sent: 23 April 2015 16:26
To: amber.ambermd.org
Subject: [AMBER] Free energy calculation of ligand binding energy: Thermodynamic integration - pmemd - single topology - vdw
Hello again,
I am trying to learn free energy calculations, however, it is much harder
than performing simple MD simulation. I would like to ask about
alchemistical calculation of mutating one ligand to another, especially
about vdw change step. When I mutated ligand1->ligand2 at lambda=0.25 a
got this result
http://postimg.org/image/adoq76m1r/
which shows some strange thing happening at a step of about 2000. So I
checked trajectory and this is what I see :
http://postimg.org/image/6ejpdhvub/
this image shows distance between ligand1 and ligand2. I am confused how
the DV/DL is beeing calculated and whether the calculation setup is right
- as clearly both ligands are interacting between each other.
I have used following setup:
icfe=1, clambda = 0.25,
ifsc=1,
timask1=':2', scmask1=':2',
timask2=':1', scmask2=':1',
crgmask=':1,2',
So my questions are following: What is the right way to calculate the vdw
change step? Is it ok to change whole ligands ( I am changing phenol to
serotonin for example)? Isn't it a problem - the result I got ?
Thank you very much for any advice!
Vlada
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Thu Apr 23 2015 - 09:30:02 PDT
