Hi Olivia,
so, you are going for the 2-step protocol?
In that case you can create the intermediate from the regular PHE (depending on your force field) and simply replace the charges with those of ALA. The disappearing atoms ("dummies") would have zero charges but still have the same bonded and vdW terms as PHE so they are "electrostatic dummies" only. One practical approach is to create a template of your own. The other option that comes to mind is to do some post-processing with parmed but I haven't looked into that yet.
I have attached two files which are part of the upcoming A9 tutorial on side-chain mutations. You would need to run the .cmd (it's a leap script) first to create INT.lib. Next you loadoff INT.lib before you read a modified PDB file where your PHE (or ALA) is replaced with the new INT residue. So for pmemd you would create prmtops for PHE/INT and INT/ALA. First step is a linear transformation (only charges change) and for the second step you would define the "dummies" as softcore atoms.
Please note that this example is for VAL->ALA and the atoms in VAL have been reordered because I am also playing with mappings. In case you can't open the attachments I have also pasted their contents below.
Cheers,
Hannes.
-----
# create a template for VAL maximally mapped to ALA
# NOTE: force field dependent, here FF14SB
source leaprc.ff14SB
INT = loadmol2 INT.mol2
set INT restype protein
set INT head INT.1.N
set INT tail INT.1.C
set INT.1 connect0 INT.1.N
set INT.1 connect1 INT.1.C
saveoff INT INT.lib
quit
-----
.<TRIPOS>MOLECULE
INT
16 15 0 0 0
PROTEIN
USER_CHARGES
****
VAL template from ff14SB, charges as in ALA with zero for dummies
.<TRIPOS>ATOM
1 N 15.1767 16.7230 17.6889 N 1 INT -0.4157
2 H 15.0727 15.7440 17.9149 H 1 INT 0.2719
3 CA 16.1687 17.0960 16.7279 CX 1 INT 0.0337
4 HA 16.8367 17.8110 17.2079 H1 1 INT 0.0823
5 CB 16.9957 15.8960 16.2529 3C 1 INT -0.1825
6 HB 16.3417 15.1760 15.7619 HC 1 INT 0.0603
7 CG1 17.7567 16.2340 15.5499 CT 1 INT 0.0603
8 CG2 17.4767 15.4240 17.1089 CT 1 INT 0.0603
9 C 15.5647 17.7420 15.5159 C 1 INT 0.5973
10 O 16.1667 18.6510 14.9469 O 1 INT -0.5679
11 HG11 18.4111 16.9550 16.0409 HC 1 INT 0.0000
12 HG12 18.3449 15.3804 15.2125 HC 1 INT 0.0000
13 HG13 17.2759 16.7064 14.6931 HC 1 INT 0.0000
14 HG21 16.7160 15.0856 17.8124 HC 1 INT 0.0000
15 HG22 18.0642 14.5708 16.7713 HC 1 INT 0.0000
16 HG23 18.1307 16.1444 17.6014 HC 1 INT 0.0000
.<TRIPOS>BOND
0 1 2 1
1 1 3 1
2 3 4 1
3 3 5 1
4 3 9 1
5 5 6 1
6 5 7 1
7 5 8 1
8 7 11 1
9 7 12 1
10 7 13 1
11 8 14 1
12 8 15 1
13 8 16 1
14 9 10 1
________________________________________
From: Olivia Pierce [olivijuly.gmail.com]
Sent: 17 July 2015 17:52
To: AMBER Mailing List
Subject: Re: [AMBER] Mutation of a protein residue in TI computation with pmemd.MPI
Hi,
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
suggestions.
Thanks!
Olivia
On Fri, Jul 17, 2015 at 2:30 AM, <hannes.loeffler.stfc.ac.uk> 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 [olivijuly.gmail.com]
> Sent: 16 July 2015 23:13
> To: amber.ambermd.org
> 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 parmed.py
> 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 - 10:30:02 PDT
