[gmx-users] Pull constrain makes simulation unstable

[Michail Palaiokostas Avramidis]

On 11/01/16 21:48, Justin Lemkul wrote:
>
>
> On 1/11/16 3:39 PM, Michail Palaiokostas Avramidis wrote:
>> Dear GMX users,
>>
>>
>> I am currently facing some stability issues when using the com
>> pulling to constrain the distance between two groups and I would
>> appreciate any help on the issue.
>>
>>
>> I am trying to simulate a lipid bilayer with a small molecule
>> introduced at several positions along the z-axis where I constrain
>> its z-movement but I allow the xy movement (z-constrain method). My
>> simulation protocol is:
>>
>>
>> 1) Run the lipid membrane with explicit water in a proper NPT
>> simulation until all properties converge
>>
>>
>> 2) Take the equilibrated gro file and by using VMD place the small
>> molecule in several different positions along the z-axis (from water
>> to bilayer core) of the bilayer (for each position I create a new gro
>> file)
>>
>>
>> 3) Then for each new gro file - position:
>>
>> 3.1) Run an energy minimization to relax any overlapping between the
>> old system and the new molecule.
>>
>> 3.2) Run the production simulation with the new molecule constrained
>> at a constant distance from the bilayer core
>>
>>
>> The problem is that I encounter inconsistent stability issues such as
>> "Water molecule xxx cannot be settled" and "LINCS WARNING
>> relative constraint deviation after LINCS ". The errors arise at
>> random positions and random setups (different molecule-membrane
>> combinations) and I cannot really identify a pattern. In all cases
>> however, the problem is not located on or around the newly introduced
>> molecule (as I would expect), but in irrelevant molecules that
>> previously worked fine.
>>
>>
>> So far I have tried:
>>
>> 1) Unconstrained simulations which run fine and indicate that the
>> system is stable on its own.
>>
>> 2) Add an extra step after 3.1 where I remove the constrain option
>> and I add a position restrain in the new molecule. Run for 1 ps to
>> basically let the system initiate. This always works flawlessly.
>> However, when I restart after the 1 ps with the COM pull constrain
>> activated and the restrain removed, the system shows me some or all
>> of the aforementioned errors.
>>
>>
>> Do you have any idea, what might be wrong? Are you aware of any
>> problems with the constrain algorithm?
>>
>>
>> The COM Pulling options I am using are:
>> pull = yes
>> pull-print-com1 = yes
>> pull-print-com2 = yes
>> pull-nstxout = 500
>> pull-nstfout = 500
>> pull-ngroups = 2
>> pull-ncoords  = 1
>> pull-group1-name = Permeant
>> pull-group2-name = Lipid
>> pull-coord1-type = constraint
>> pull-coord1-geometry = distance
>> pull-coord1-groups = 1 2
>> pull-coord1-dim = N N Y
>> pull-coord1-init = 0.01
>>
>>
>> I am sorry for the long e-mail and thank you in advance for any help
>> you can give me.
>>
>
> Your pull settings specify pull-coord1-init = 0.01, which indicates
> that the constraint distance is to be 0.01 nm separation from the
> bilayer ("Lipid" group).  This likely triggers an immediate crash
> because the constraint length at t=0 is much larger.  Remember that
> the constraint is rigid.  Probably what you want in the case of
> multiple locations along the reaction coordinate is:
>
> pull-coord1-start = yes    ; use starting coordinates to define length
> pull-coord1-init = 0.0
>

Hi Justin,

thanks a lot for your answer. Actually, the problem was on the
definition of the groups. I created the indexes from the PDB but until I
reached the after minimization gro, the atom numbers completely changed,
creating in that way huge distances that obviously crashed. Took some
time to discover this detail.

Also, I had misunderstood how the above commands worked. I believe that
the documentation  needs a bit more explanation or at least some
examples, but anyway, thanks once again for your time and excellent
tutorials.

Best Regards,
Michail

> My tutorial may be helpful in explaining these settings:
>
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html
>
>
> -Justin
>