Re: [AMBER] Mutation of a protein residue in TI computation with pmemd.MPI

From: Olivia Pierce <>
Date: Fri, 17 Jul 2015 12:52:02 -0400


Thanks Dan and Hannes for your comments! I also thought about placing the
dummy atoms into the places of the disappearing atoms of Phe, but the
problem I thought was that tleap might complain - the mutating residue name
is Ala but obviously it has more atoms than what Ala should have. Do you
think this would not be the problem? I would appreciate any further


On Fri, Jul 17, 2015 at 2:30 AM, <> wrote:

> Dan has already told you how to principally solve this. But the
> description of what you are planning to do does not seem to match your
> input file. I understand that you want to do an elestrostatic
> transformation only first but what crgmask does is to only set the atom
> charges to zero. Apparently you switch off the charges of ALA completely.
> If that is really your plan you would do a linear transformation of
> ALA(charge) to ALA(uncharged). Although if you mutate PHE->ALA the steps
> would seem to be: 1) PHE(charged)->PHE(uncharged); 2)
> PHE(uncharged)->ALA(uncharged); 3) ALA(uncharged)->ALA(charged).
> An electrostatic only transformation would (currently) require you to
> create and intermediate that has all vdW and bonded parameters of PHE but
> the charges of ALA. As you would do that in a linear transformation you
> would need to fill up all disappearing atoms of PHE with dummies in ALA.
> These dummies are then defined as softcore atoms in the second step.
> Overall, this protocol seems to be more attractive to me but requires more
> work to set up (I am writing a tool to do exactly this but it is still only
> dealing with non-covalently bound molecules yet). Alternatively, pmemd
> would implement lambda paths which would make this much simpler. Dan, is
> this still on your TODO list?
> ________________________________________
> From: M Olivia Kim []
> Sent: 16 July 2015 23:13
> To:
> Subject: [AMBER] Mutation of a protein residue in TI computation with
> pmemd.MPI
> Hi,
> I am trying to run a FEP simulation for mutation of a protein residue
> using the pmemd.MPI module. I'm mutating a Phe to Ala - following the
> Amber14 manual, I prepared the prmtop and inpcrd files using
> where the redundant bonding terms for the overlapping residues are deleted.
> So the final pdb for my system looks like that protein consists of residues
> 1-177 and the residues 178 is Ala (separated by TER), which is the mutant
> for the Phe in the WT.
> I was first trying to run the non-soft core simulation, where the atomic
> charges of the WT protein residue are changed to the charges of the mutated
> residue along with lambda. However, since the atom numbers of the WT
> residue and mutant are different, I couldn't even run the minimization. The
> part corresponding to TI in my minimization input file is:
> icfe = 1, clambda = 0.0,
> ifsc = 0,
> timask1 =
> '.1019,1020,1021,1022,1023,1024,1025,1026,1027,1028,1029,1030,1031,1032,1033,1034,1035,1036,1037,1038',
> timask2 = '.2780,2781,2782,2783,2784,2785,2786,2787,2788,2789',
> crgmask = '.2780,2781,2782,2783,2784,2785,2786,2787,2788,2789',
> /
> And the error message I got is:
> TI Mask 1
> .1019,1020,1021,1022,1023,1024,1025,1026,1027,1028,1029,1030,1031,1032,1033,1034,1035,1036,1037,1038;
> matches 20 atoms
> TI Mask 2 .2780,2781,2782,2783,2784,2785,2786,2787,2788,2789; matches
> 10 atoms
> ...
> ERROR: timask1/2 must match the same number of atoms for non-softcore run
> Is there any way I can correct my input or prmtop file so that I can run
> this simulation? Or is this type of simulation (mutation of a protein
> residue to another that has different number of atoms) not supported by
> pmemd version of TI in Amber yet? I'll look forward to any advice or
> comments. Thanks in advance!
> Best,
> Olivia
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Received on Fri Jul 17 2015 - 10:00:02 PDT
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