You've gotten good advice from a couple other people, so I'll point out a
few other details I noticed.
On Sat, May 4, 2013 at 5:08 AM, Angelica Parente <aparente.stanford.edu>wrote:
> Hi all,
>
> I've been very frustratingly trying to run MMPBSA on ligands (cis and
> trans isomers of the same molecule) I've docked into my protein, but I'm
> having issues with invalid unsolvated complex prmtop files. I have a
> feeling this might be because I had my ligand numbered as the default '900'
> and had forgotten to change it to '204' (restraint_mask is set at :1-203
> for the total # of protein residues), but I've come across this error quite
> often with other ligands and have not found a solution. I've copy pasted my
> input files, some for cis and some for trans, but I used the same method
> for both.
>
Numbering in the PDB file does not correspond to numbering in the prmtop
necessarily. The topology files number residues sequentially. If your PDB
has residues 1-203 and residue 900 (missing 204 to 899), then the residues
in your topology file (and therefore recognized by MMPBSA.py) will be
numbers 1-204, where residue 900 in the PDB is residue 204 in the prmtop.
> I've tried looking at the trajectories (~34000 frames, 64ns) in VMD, but
> VMD crashes after loading in about ~7000 frames. From what I can see, the
> trajectory looks fine, but I haven't been able to look at it in depth. Do
> these errors might possibly mean that my solvated complex prmtop files are
> not correct, and that I need to start my simulations over? This has worked
> for other ligands sharing the same general structure, but the MMPBSA
> results I get for those are very strange (PB total free energy difference
> is ~ +1000kcal/mol due to high non-polar free energy components, and GB is
> -42kcal/mol, and sometimes the GB VDW energy skyrockets to very high values
> before coming back to the -42kcal/mol).
>
>
> Initially, I get the following error:
>
> Beginning GB calculations with
> /home/mlawrenz/Programs/amber12/bin/mmpbsa_py_energy
> calculating complex contribution...
> CalcError: /home/mlawrenz/Programs/amber12/bin/mmpbsa_py_energy failed
> with prmtop nv1-trans-docked-1-complex.prmtop!
>
> Upon further inspection, here is what I see in the
> _MMPBSA_complex_gb.mdout.0 file:
>
> Reading parm file (../../nv1-trans-docked-1-complex.prmtop)
> title:
> default_name
> mm_options: e_debug=2
> mm_options: gb=2
> mm_options: rgbmax=25.000000
> mm_options: gbsa=1
> mm_options: surften=0.007200
> mm_options: cut=999.000000
> mm_options: epsext=78.300000
> mm_options: kappa=0.103952
> Error: gb>0 is incompatible with periodic boundary conditions.
> Error: To use this method set IFBOX in the PRMTOP file to 0.
> Error: See http://ambermd.org/formats.html
>
>
> IFBOX is set to 1 in my complex prmtop files because I generated them in
> leap with the following input file:
>
> source leaprc.ff99SBildn
> source leaprc.gaff
> best= loadpdb ./equil-apo.pdb
>
> check best
> set best tail null
> set best head null
> setbox best vdw
> #solvatebox best TIP3PBOX 10
> #addions2 best Na+ 0
> saveamberparm best ./nv1-trans-docked-1-complex.prmtop
> ./nv1-trans-docked-1-complex.inpcrd
> savepdb best ./nv1-trans-docked-1-complex.amber.pdb
>
It's important to know what each command is doing, IMO. The head/tail
setting probably does nothing. In fact, it may be a bad thing. If there
is no head or tail atom, your commands do nothing. If there is, then your
residue expects to be an internal residue that will probably have dangling
bonds if you eliminate the head/tail definitions.
The command that is causing the error message you've mentioned is the
"setBox" command. In general, setBox is rarely needed (at least in my
experience). What it does is set up a periodic box around your system
making sure that the box contains either every atomic center or every atom
up to its vdW radius. This sets IFBOX to 1 even if there is no solvent.
This is not what you want for implicit solvent calculations (and is what
caused the error you saw).
The solvateX commands automatically add a periodic box, which is why I said
you rarely need that command. Only if you read in a PDB that has already
been solvated do you need to use this command (or if you want to set up
some kind of periodic simulation like crystal simulations, perhaps).
To generate the unsolvated prmtop file, I just comment out the 'solvatebox'
> and 'addions' lines.
>
>
> To generate the ligand prmtop, I use the following leap input file:
>
> source leaprc.ff99SBildn
> source leaprc.gaff
>
> loadamberparams novo-mod-1-cis_pdb.frcmod
> loadamberprep novo-mod-1-cis_pdb.prep
>
> ligand= loadpdb ./novo-mod-1-cis.pdb
>
> check ligand
> set ligand tail null
> set ligand head null
> setbox ligand vdw
> #solvatebox ligand TIP3PBOX 12
> #addions2 ligand Na+ 0
> saveoff ligand nv1.lib
> saveamberparm ligand ./nv1-cis.prmtop ./nv1-cis.inpcrd
> savepdb ligand ./nv1-cis.amber.pdb
>
> After trying Ante-MMPBSA to generate unsolvated complex, receptor, and
> prmtop files thinking this might fix my problem, I get the following error:
>
What was your ante-MMPBSA.py command? If the topology files are not
created correctly, then best case MMPBSA.py will detect the error and fail.
Worst case, you'll just get garbage results.
>
> Running MMPBSA.MPI on 24 processors
>
In addition to what Dave mentioned, try running the serial version of
MMPBSA.py. It's always easier to debug on a small number of processors
and a small number of frames. Once you have that working, then you should
scale up.
Reading command-line arguments and input files...
> Loading and checking parameter files for compatibility...
> PrmtopError: Couldn't predict mask from topology files!
> Your ligand residues must be sequential in your complex.
> There are likely problems with your topology files if this is not the case.
> Error occured on rank 1.
>
>
For most people, this error message indicates an error and/or inconsistency
in your topology files. (Specifically, this is really only possible if
your designated 'ligand' residue is composed of multiple molecules).
Good luck,
Jason
--
Jason M. Swails
Quantum Theory Project,
University of Florida
Ph.D. Candidate
352-392-4032
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Received on Sat May 04 2013 - 17:30:02 PDT
