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.
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
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:
Running MMPBSA.MPI on 24 processors
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.
Exiting. All files have been retained.
--------------------------------------------------------------------------
MPI_ABORT was invoked on rank 1 in communicator MPI_COMM_WORLD
with errorcode 1.
NOTE: invoking MPI_ABORT causes Open MPI to kill all MPI processes.
You may or may not see output from other processes, depending on
exactly when Open MPI kills them.
--------------------------------------------------------------------------
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 17.
Exiting. All files have been retained.
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 18.
Exiting. All files have been retained.
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 19.
Exiting. All files have been retained.
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 21.
Exiting. All files have been retained.
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 7.
Exiting. All files have been retained.
Thank you for your help!
Angelica C. Parente
Graduate Student in Biophysics
Stanford University School of Medicine
aparente.stanford.edu
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Received on Sat May 04 2013 - 02:30:03 PDT
