Re: hBond colvars and patching

From: Francesco Pietra (chiendarret_at_gmail.com)
Date: Mon Mar 07 2011 - 00:12:54 CST

Hi Giacomo:
OK, this confirms authoritatively what I imagined for a restraint.

>From this firm position, at large, I certainly need to restrain
through colvars the hydrogen bonds and partners. This is a must for
Cl-, which - unlike in nature - has no pool to replace it when it
leaves the protein. My problem is to build correctly the hydrogen
bonds in the frame of VMD/NAMD. Let me detail how I did with the GLUP
patches. Starting from negatively charged GLU, in "Autopsf - Add
Patch" I entered, for example:

Patch type: GLUP, Segment 1: P1, Residue 1: 277

this led to the added proton being in the unfavorable position that I
described, although the psf/pdb could be minimized and heated.

Previously, I also filled in "Autopsf - Add Patch", in addition to the above,

Segment 2 (opt) ... Residue 2:....

for the intended acceptor of Segment 1, Residue 1

at no avail as far as the H-bond is concerned. This latter action in
an imitation of the DISU patch, where both S atoms of the S-S bond are
set in.
************

What I hope is that there is a mistake in my procedure, and be
corrected about. Otherwise suggestions how to set correctly H-bonds in
VMD/NAMD along a different route. As I said, I came to NAMD with
correct PDB files - from REDUCE or other - as far as H-bonds are
concerned. However, files strictly respecting PDB rules and, in
addition, also with some non CHARMM naming, which I tried to correct.
I was unable to arrive at workable psf/pdb along this route. Finally,
I could also correct the autopsf.pdb by repositioning the proton in
between GLU and the acceptor, be that the conjugate base or Cl-, with
a graphic package. However, this also failed - in my hands - to arrive
at workable psf/pdb.

thanks
francesco

On Mon, Mar 7, 2011 at 5:57 AM, Giacomo Fiorin
<giacomo.fiorin_at_temple.edu> wrote:
> Hi Francesco, use the hBond colvar component only if you need to apply a
> restraint or compute the potential of mean force for breaking / forming that
> hydrogen bond.
>
> But the starting point should always be a reasonable protonation state, if
> that's not the most stable for any reason, there isn't a restraint that can
> fix that.
>
> Do you think it's the former or the latter?  If you run without any
> additional restraints (colvars or not) and the structure is not stable, then
> the protonation state is not good, and that should be corrected regardless.
>
> Giacomo
>
>
> ---- ----
>   Dr. Giacomo Fiorin
>   ICMS - Institute for Computational Molecular Science - Temple University
>   1900 N 12 th Street, Philadelphia, PA 19122
>   giacomo.fiorin_at_temple.edu
> ---- ----
>
>
>
> On Sun, Mar 6, 2011 at 3:05 PM, Francesco Pietra <chiendarret_at_gmail.com>
> wrote:
>>
>> Hello:
>> lost my mail, taken the essential from the VMD archive.
>>
>> <<in setting "hBond" in colvars for GLUP-GLU and
>> GLUP-chloride_anion hydrogen bonds, should the acidic proton of
>> neutral GLU be present in the PDB file, as obtained from GLUPP
>> patching?>>
>>
>> This question arose from my problems in getting the correct
>> orientation of the added proton. I have now recreated the psf/pdb from
>> scratch and - in all cases - the added proton goes into the least
>> favorable position with respect to the intended acceptor. As the
>> H-bond is indirectly evident from my 2A X-ray diffraction data, and
>> the importance of the H-bond is clearly shown by my physiological
>> experimentation at different pH values (and the good ones suggest 50%
>> protonation of GLU), I am quite concerned. If it is an error in my
>> procedure, I would be happy, however patching does not leave much room
>> for intervention. This is why I tried to come to NAMD with already
>> protonated titrable residues, got from REDUCE or other software, or by
>> adjusting the conformations manually on psf/pdb, which created
>> problems to NAMD.
>>
>> What happens (both toward ASP or other acceptor) is that the acidic
>> proton is anti to the desired acceptor. In one case it is on the
>> "wrong" oxygen, thus even farther away. Interatomic distances and
>> orientations from X-ray diffraction data are standard for stron
>> H-bonds.
>>
>> Before redoing psf/pdb, I had minimized and heated the ensemble in
>> lipid bilayer surrounded by TIP3. Should the correct orientation in
>> H-bond result from extensive MD?
>>
>> thanks
>> francesco pietra
>>
>> Assuming correct procedure, how now with hBond colvar? Should that put
>> the matter in order, or hBond colvar is to be used in place of GLU
>> patching?
>>
>
>

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