On 1/12/17 11:20 PM, Mohsen Ramezanpour wrote:
On Thu, Jan 12, 2017 at 8:36 PM, Justin Lemkul <jalem...@vt.edu> wrote:
On 1/12/17 10:21 PM, Mohsen Ramezanpour wrote:
On Thu, Jan 12, 2017 at 6:31 PM, Justin Lemkul <jalem...@vt.edu> wrote:
On 1/12/17 7:47 PM, Mohsen Ramezanpour wrote:
On Thu, Jan 12, 2017 at 4:24 PM, Justin Lemkul <jalem...@vt.edu> wrote:
On 1/12/17 3:18 PM, Mohsen Ramezanpour wrote:
Dear Gromacs users,
For parameterization of a molecule in Charmm36, I have got the QM
scanning
and partial charges from GAMMP server. However, the fitted parameters
are
not good enough.
That's very surprising. What's wrong with what GAAMP gave you?
The dihedral has two local minima in both QM and fitted ones both from
GAAMP. The angle for the minima are okay but the corresponding depths
are
not.
In fact, the depth for the first local minimum is larger than second one
in
QM, while the situation is reverse in MM profile with fitted parameters.
This makes the dihedral to be more (statistically) in wrong angle (in
local
minimum which is not the most favourable one).
GAAMP, unfortunately, did not work well with my case (some critical
partial
charges and critical dihedrals).
I decided to do the MM scanning and try to get better parameters for the
dihedral.
Unfortunately, I do not have any experience with this part, and I
could
not
find any tutorial for how to do this in Gromacs.
I was wondering if you are aware of any tutorial which could help me
to
overcome this challenging step.
Tutorial (CGenFF theory is the same as CHARMM, by design):
http://mackerell.umaryland.edu/~kenno/cgenff/download.php#tutor
Fitting program and other resources:
http://mackerell.umaryland.edu/~kenno/lsfitpar/
http://mackerell.umaryland.edu/ff_dev.shtml
Obviously, these are all CHARMM-centric approaches and frankly the
modules
within CHARMM make parametrization rather straightforward (not "easy,"
mind
you, but straightforward). Since I began working with CHARMM, it has
become indispensable in my daily routine.
If you want to do things in GROMACS, the main issue is that you will
have
to do MM scans in a more manual fashion, by restraining the target
dihedrals (very strongly) in a series of configurations (typically at
intervals of 15 degrees over a full rotation) while allowing the rest
of
the molecule to relax to match the QM.
If I got it right, I must do EM on the molecule while only the desired
dihedral is fixed in a specific angle. Which aspect should match with
QM?
If you mean structurally, what is the criteria for matching (RMSD?.)?
"Match" in this case means "treat equivalently," therefore only one
constraint (restraint in the MM) should be applied while allowing the
rest
of the molecule to relax freely. You do have a difficult case because
each
of your molecules is symmetric; this means the same dihedral term is
affecting multiple torsions.
So, probably I should 4 dihedrals and try to optimize all at once?!(
because all 4 dihedrals of O-C-CH2-CH3 seems equivalent to me). Am I
right?
No, there are 2 O-C-CH2-CH3 dihedrals, not 4.
How come? :-) there are two ethyls and two oxygens in the ring. Each ethyl
forms two dihedrals (one with each oxygen).
Thus, there would be 4 dihedrals. And all of these 4 should be equivalent.
Sorry, mentally jumping ahead. By atom typing, yes, there are 4 that are the
same, but there are still only 2 equivalent rotatable bonds that need to be
addressed. So you can define the rotation in the PES as either of the two for a
given rotatable bond, they're redundant. So choose one and fit to it. You are,
in any case, doing a PES of the entire molecule, so the fitting accounts for the
redundancy.
-Justin
Deactivate the restraint, obtain the potential energy of the molecule
via
mdrun -rerun and plot as a function of the dihedral.
This should be a zero step EM, right? The molecule should not be allowed
to
change its conformation.
No, a zero-step MD. EM actually changes the coordinates before step
zero.
A bit of shell scripting and careful topology modification and this can
be done.
Two more questions on this part:
1) I am using the QM scanning data and partial charges from GAAMP. When
I
do this MM scanning, do I need to exclude any 1-4 interactions or I can
behave this dihedral as other dihedrals?
1-4 interactions are always at full strength in CHARMM.
2) this dihedral is part of a lipid.
Do I need to do these on only "one Lipid in vacuum" or
OR
on all lipids in "a bilayer in vacuum" or in a "bilayer in solvent"
I think it should be "one Lipid in vacuum".
One model compound in vacuum, from which you will construct the lipid.
How if this compound (which is small part of the lipid) is charged?
Should
it be still in vacuum?
Yes. The fact that a molecule is irrelevant except for when considering
the dipole moment.
Is there any specific consideration to be made in zero-step MD? e.g. a big
simulation box or specific parameter in .mdp file?
Infinite cutoffs, no PBC.
-Justin
--
==================================================
Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow
Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201
jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul
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==================================================
Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow
Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201
jalem...@outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul
==================================================
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