[gmx-users] Pull constrain makes simulation unstable

[Justin Lemkul]

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

My tutorial may be helpful in explaining these settings:

http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html

-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

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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