[gmx-users] Umbrella sampling

[Justin Lemkul]

On 11/25/17 3:59 PM, rose rahmani wrote:
> On Sat, Nov 25, 2017 at 11:46 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>> On 11/25/17 3:07 PM, rose rahmani wrote:
>>
>>> Oh sorry this is .mdp file:
>>>
>>> DEFINE                   = -DPOSRES
>>>
>> What are you restraining? This seems counterproductive, and by default
>>> (unless you've hacked the topology), this is going to restrain your
>>> protein, which is definitely wrong.
>> yes, protein.you mean i should remove it and don't restraint anything? and
>> for npt(previous step) run too?

What is the purpose of a restraint? To prevent motion. What is your 
objective? To cause motion of your protein towards a surface. Does it 
make sense to restrain the protein during this process?

Equilibration is a separate matter.

>>> integrator               = md
>>> dt                       = 0.001
>>> nsteps                   = 2000000
>>> nstxout                  = 0
>>> nstvout                  = 0
>>> nstfout                  = 0
>>> nstlog                   = 500
>>> nstenergy                = 1000
>>> nstxtcout                = 1000
>>> rlist                    = 1.5
>>> rcoulomb                 = 1.5
>>> rvdw                     = 1.2
>>>
>> Again, I am suspicious of these cutoffs. What force field are you using?
>>
>> AMBER99

Then yes, those cutoffs are wrong. This is also a very old force field, 
and newer/better variants of it exist. Refer to the literature to find 
the right cutoffs for the parameter set you decide upon. This is not a 
trivial matter.

>> coulombtype              = pme
>>> cutoff-scheme            = group
>>> vdwtype                  = Switch
>>> rvdw_switch              = 1.0
>>> pcoupl                   = no
>>> gen-vel                  = yes
>>> gen-temp                 = 0
>>> gen-seed                 = 173529
>>> constraints              = h-bonds
>>> pbc                      = xy
>>> freezegrps               = WAL ZnS
>>> freezedim                = Y Y Y Y Y Y
>>> energygrp-excl           = WAL WAL ZnO ZnO
>>> energygrps               = SOL WAL ZnO Protein NA CL
>>> nwall                    = 2
>>> wall-atomtype            = C C
>>> wall-type                = 9-3
>>> wall-density             = 150 150
>>> wall-ewald-zfac          = 3
>>> ewald-geometry           = 3dc
>>> fourierspacing           = 0.12
>>> tcoupl                   = v-rescale
>>> tc-grps                  = System
>>> tau-t                    = 0.1
>>> ref-t                    = 300
>>> pull                    = yes
>>> pull_ngroups            = 2
>>> pull_ncoords            = 1
>>> pull_group1_name        = ZnS
>>> pull_group2_name        = Protein-H
>>>
>> You can probably just use the whole protein here, though I doubt it makes
>> much difference.
>>
>> pull_coord1_type        = umbrella      ; harmonic biasing force
>>> pull_coord1_geometry    = distance      ; simple distance increase
>>> pull_coord1_groups      = 1 2
>>> pull_coord1_dim         = N N Y
>>> pull_coord1_rate        = 0.001
>>>
>> Here's your problem. With a positive pull rate, you are instructing mdrun
>>> to increase the COM distance between the protein and the ZnS surface. If
>>> you want them to come closer, you need a negative value here, to decrease
>>> the distance as a function of time. Of course, this all goes out the window
>>> if your protein is restrained, as suggested above.
>>
> oh, i've got it.
> you restrained chain B in tutorial but i shouldn't because ZnS is freezed?

No, I restrained a chain in my protein to mimic the stability of 
(physiologically) much larger systems. People typically fail to read my 
paper that is the basis of that tutorial, in which this concept is 
explained. Perhaps I need to add a bold, flashing warning that people 
should not be blindly following the method.

-Justin

-- 
==================================================

Justin A. Lemkul, Ph.D.
Assistant Professor
Virginia Tech Department of Biochemistry

303 Engel Hall
340 West Campus Dr.
Blacksburg, VA 24061

jalemkul at vt.edu | (540) 231-3129
http://www.biochem.vt.edu/people/faculty/JustinLemkul.html

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