Dear all,
I am trying to calculate the free energy of binding of a ligand to a
protein that has around 6000 atoms. Needless to say running NMode on the
whole protein takes forever, the minimization gets stuck very frequently
and it also doesn't seem like the drms is going any lower after a while.
I am looking into truncating the trajectory using the method described here:
http://www.teokem.lu.se/~ulf/Methods/mm_pbsa.html
I would like to know if the code changes outlined there are still the code
changes that would be needed in the amber14 code. I am also unsure as to
why so many confusing steps seem to be needed for this to work.
Wouldn't taking the following steps be enough:
1) Determine which residues are within 12 angstroms of the ligand (I would
personally do this by using the VMD command same residue as within 12 of
ligand) and which are within 8 of the ligand in the same way.
2) Truncate the trajectory in cpptraj:
parm full_system.parm7
trajin full_system.nc
strip : "residues that are not within 12 of ligand" outprefix trunc
trajout trunc.nc netcdf
3) Change the mm_pbsa_createinput file so that it writes input files for
nmode in which the residues between 8 and 12 Angstroms are restrained.
4) Remove all the lines in leaprc.ff14SB under addPdbResMap. *--- Is this
really necessary? *Wouldn't we want the input files for NMode to consist of
the ligand + the residues within 12 Angstroms of it, capped nicely at their
loose ends? Or just the residues within 12 Angstroms of the ligand in the
case of the receptor, but with their loose ends capped nicely? Or is it
that by truncating the trajectory, the residues are not capped, in which
case there would be a disagreement between the number of atoms in the
topology file and that in the input files?
5) Make nmode able to run thermo analysis even if belly is used by:
In nmode.f (around line 296):
write(6,*) 'Thermo analysis not supported for belly calc.'
! Code added by Jacob Kongsted 2007 for new MM/PBSA entropy
! JK
nvecs = 3*natsys - 6
call thermo(natsys,nvecs,ilevel,x(mx),x(mamass),x(mcval), &
x(mh),x(mh+ns3),x(mh+2*ns3), &
x(mh+3*ns3),t,patm)
! End of new code
In make_crd_hg.f:
parameter (NMO=400)
Lastly, I am not sure why in the procedure I was referring to, the authors
were trying to include some water molecules in the buffer zone. Were those
crystallographic waters? Otherwise I am not sure why there would be waters
in the trajectory in the first place. Isn't the first thing that MM-PBSA
does to strip the trajectories of water molecules?
Thank you a lot!
Laura
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Received on Thu Apr 16 2015 - 12:00:03 PDT
