Re: Fwd: Atoms too fast/periodic cell too small with ABF protein-ligand

From: Francesco Pietra (chiendarret_at_gmail.com)
Date: Thu Jun 29 2017 - 08:47:59 CDT

Hi Giacomo:
Thanks for your advice.

I'll look for, as soon I have the time, for an alternative to

# WRAPPING

wrapAll on

by continuing the 58.2ns unbiased MD. I also assume that in your advice it
is implied the instability of the system under both ABF and FEP might
originate from a wrong computation of the center of mass.

On the other hand, wrapAll is what is set in the tutorial protein-ligand
for both ABF and FEP.

francesco

On Wed, Jun 28, 2017 at 6:35 PM, Giacomo Fiorin <giacomo.fiorin_at_gmail.com>
wrote:

> Hi Francesco, wrapAll is not recommended for a system where more than one
> molecule is involved in the variables' definition:
> http://colvars.github.io/colvars-refman-namd/colvars-refman-
> namd.html#x1-160004.3
>
> Again, the computation of a center of mass for a group requires unwrapped
> coordinates. I would double check that the same exact configuration is
> being loaded into VMD, against a NAMD simulation with 0 steps.
>
> Giacomo
>
>
>
> On Tue, Jun 27, 2017 at 3:46 AM, Francesco Pietra <chiendarret_at_gmail.com>
> wrote:
>
>> Hi Giacomo:
>> I am using for ABF the last frame (.xsc file) of MD equilibration
>> generated without PBCs enabled in NAMD config file. That config file
>> only had:
>>
>> wrapNearest no
>> wrapAll on
>>
>> If I measure directly the distance between the centers of mass of protein
>> and ligand for that frame:
>>
>>
>>> >Main< (francesco) 33 % set selprot [atomselect top "protein"]
>>> atomselect3
>>> >Main< (francesco) 34 % measure center $selprot
>>> 326.3038024902344 453.4432678222656 342.5987243652344
>>> >Main< (francesco) 35 % set sellig [atomselect top "segname SAA1"]
>>> atomselect4
>>> >Main< (francesco) 36 % measure center $sellig
>>> 329.97216796875 441.479736328125 317.9831237792969
>>>
>> >Main< (francesco) 37% set dist [veclength [vecsub [measure center
>> $selprot] [measure center $sellig]]]
>> 27.613597797130065
>> >Main< (francesco) %
>>
>>
>> I get a result (27.6) different from "cv printframe" by loading that
>> NAMD frame to VMD (18.9).
>>
>> Should any of these conditions be unsuitable for ABF, then, without a
>> complete reeducation, it will be difficult for me carrying out an ABF
>> for protein-ligand. However, I am strongly interested in that particular
>> protein-ligand system, I spend a lot of time in parameterizing the ligand.
>> I imagine that with FEP (not yet attempted) I'll be faced by samilar
>> problems.
>>
>> francesco
>>
>>
>>
>> On Mon, Jun 26, 2017 at 6:32 PM, Giacomo Fiorin <giacomo.fiorin_at_gmail.com
>> > wrote:
>>
>>> Hi Francesco, when distances between groups of atoms are involved, it is
>>> really important to check that the PBCs are the same in both VMD and NAMD.
>>>
>>> Giacomo
>>>
>>> On Mon, Jun 26, 2017 at 12:24 PM, Francesco Pietra <
>>> chiendarret_at_gmail.com> wrote:
>>>
>>>> I also run the same ABF (rmsd all atoms of the ligand less methyl
>>>> hydrogens) with colvar "r" = 18.9 from cv printframe (unlike the directly
>>>> measured 27.6 with previous ABFs). In all cases, I took the colvars values
>>>> from the last frame of the 58.2ns MD, not averages along the whole
>>>> simulation)
>>>>
>>>>
>>>> Main< (Conformation:5xxf-SAA1) 28 % cv printframe
>>>>> 0 1.88926419197828e+01 5.22845307973583e+01
>>>>> -3.39612142392650e+01 9.26730407864645e+00 1.01135055762437e+02
>>>>> -5.05311208874754e+01 0.00000000000000e+00 0.00000000000000e+00
>>>>>
>>>>> >Main< (Conformation:5xxf-SAA1) 29 %
>>>>>
>>>>> >Main< (Conformation:Bound_5xxf-SAA1-allH_except_methyl_H) 33 % cv
>>>>> printframelabels
>>>>> # step r Theta
>>>>> Phi Psi theta
>>>>> phi RMSD r_RMSD
>>>>>
>>>>
>>>> The immediate (step 0) error was again atoms moving too fast, this time
>>>> one heavy atom and one H-atom of the ligand.
>>>>
>>>> f
>>>>
>>>> ---------- Forwarded message ----------
>>>> From: Francesco Pietra <chiendarret_at_gmail.com>
>>>> Date: Mon, Jun 26, 2017 at 12:28 PM
>>>> Subject: Fwd: Atoms too fast/periodic cell too small with ABF
>>>> protein-ligand
>>>> To: NAMD <namd-l_at_ks.uiuc.edu>
>>>>
>>>>
>>>> I must add that the attempted ABF was "Conformation:Bound". For rmsd
>>>> for the ligand I had chosen all heavy atoms.
>>>> By choosing all atoms of the ligand, except hydrogens at the methyl
>>>> groups, the simulation also crashed at the first step, this time for two H
>>>> atoms of the protein, one (HG1) very far from the ligand, the other one
>>>> (HA) close to the ligand.
>>>>
>>>> With "Conformation:Unbound" the ABF went to completion without errors.
>>>>
>>>> Hope this helps suggesting what to do.
>>>>
>>>> As I said, there was no problem with MD equilibration for this system,
>>>> at the same ts=1.0fs, along a trajectory of during 58.2ns.
>>>>
>>>> francesco
>>>>
>>>>
>>>> ---------- Forwarded message ----------
>>>> From: Francesco Pietra <chiendarret_at_gmail.com>
>>>> Date: Sun, Jun 25, 2017 at 12:56 PM
>>>> Subject: Atoms too fast/periodic cell too small with ABF protein-ligand
>>>> To: NAMD <namd-l_at_ks.uiuc.edu>
>>>>
>>>>
>>>> Hello:
>>>>
>>>> I am attempting a protein-ligand ABF, following the 2017 tutorial, by
>>>> using a 58.2ns problemless equilibrated system (ts=1.0 fs, bond restriction
>>>> on water only) in a TIP3P water box on a main pure-CPU cluster. Rather
>>>> large protein, organic ligand as accurately parameterized as I could, by
>>>> fitting torsions and water interaction.
>>>>
>>>> I am experiencing immediate "atoms moving too fast" (two H atoms of the
>>>> ligand) when using a linux 4-core cpu desktop, or "periodic cell has become
>>>> too small" on a linux GPU workstation. At the moment I have no access to
>>>> the cluster.
>>>>
>>>> I used ts=1.0 fs, i.e. no bond restriction, except for TIP3P water, as
>>>> in the equilibration.
>>>>
>>>> As a possible cause, that I was unable to verify, is the setting of
>>>> Euler and polar angle in the colvars definition. That is , I used the
>>>> following values from "cv printframe"
>>>>
>>>> >Main< (Conformation:5syf-SAA1) 28 % cv printframe
>>>>> 0 1.88926419197828e+01 5.22845307973583e+01
>>>>> -3.39612142392650e+01 9.26730407864645e+00 1.01135055762437e+02
>>>>> -5.05311208874754e+01 0.00000000000000e+00 0.00000000000000e+00
>>>>>
>>>>
>>>> by discarding the first two, and using the directly measured
>>>> intercenter distance of 27.6A in place of 18.89 from printframe, i.e., as
>>>> follows:
>>>>
>>>>
>>>> harmonic {
>>>> colvars r
>>>> forceConstant 0.0
>>>> centers 27.6 # OK measured
>>>> }
>>>>
>>>>
>>>> harmonic {
>>>> colvars Theta
>>>> forceConstant 0.0
>>>> centers 52.3 # from printframe
>>>> }
>>>>
>>>>
>>>> harmonic {
>>>> colvars Phi
>>>> forceConstant 0.0
>>>> centers -40.0 # from printframe
>>>> }
>>>>
>>>>
>>>> harmonic {
>>>> colvars Psi
>>>> forceConstant 0.0
>>>> centers 9.27 # from printframe
>>>> }
>>>>
>>>>
>>>> harmonic {
>>>> colvars theta
>>>> forceConstant 0.0
>>>> centers 101.1 # from printframe
>>>> }
>>>>
>>>>
>>>> harmonic {
>>>> colvars phi
>>>> forceConstant 0.0
>>>> centers -50.5 # from printframe
>>>> }
>>>>
>>>> Should this assignment of colvars be correct, where to look for the
>>>> causes of the instability of the system?
>>>> I must confess that I am the first time at such an ABF beyond the
>>>> tutorial
>>>>
>>>> Thanks for advice
>>>>
>>>> francesco pietra
>>>>
>>>>
>>>>
>>>
>>>
>>> --
>>> Giacomo Fiorin
>>> Associate Professor of Research, Temple University, Philadelphia, PA
>>> Contractor, National Institutes of Health, Bethesda, MD
>>> http://goo.gl/Q3TBQU
>>> https://github.com/giacomofiorin
>>>
>>
>>
>
>
> --
> Giacomo Fiorin
> Associate Professor of Research, Temple University, Philadelphia, PA
> Contractor, National Institutes of Health, Bethesda, MD
> http://goo.gl/Q3TBQU
> https://github.com/giacomofiorin
>

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