[gmx-users] Do I need position restraint for umbrella sampling?

[Yoo Chan Myung]

Dear Justin,

Thank you for your advice.

I tried to restraint the wandering peptides, because umbrella MD results showed 'missing z=0.? ‘ errors when I run WHAM analysis.

If I narrow the sampling space from 0.2nm to 0.1nm for umbrella MD simulation, could it be a better way to solve the ‘missing z=0.?’ errors than using position restraint to keep the wandering peptides in there position according to their initial z coordinates?

Thanks again.

Regards,
Yoochan
> On Sep 20, 2016, at 4:32 AM, Justin Lemkul <jalemkul at vt.edu> wrote:
> 
> 
> 
> On 9/18/16 11:35 PM, Yoo Chan Myung wrote:
>> Dear gmx users,
>> 
>> I'm trying to simulate membrane penetration with peptide(octamer) using
>> GROMACS-5.1.2. and I referred the Umbrella Sampling tutorial by Dr. Justin
>> Lemkul.
>> 
>> After 100 ps umbrella_NPT run, peptides confirmations are still kept in
>> their initial coordinates. However, after 10ns of umbrella_MD, I cannot get
>> reliable results for WHAM analysis because the confirmations are quite
>> deviated from the umbrella_NPT structures.
>> (plz, refer two results,
>> https://www.dropbox.com/s/maqwjww8nozmcn6/q_a.jpg?dl=0)
>> 
>> So, my question is should I have to use position restraint for moving
>> ligands? or just extend simulation time for umbrella_NPT to get equilibrium
>> structures for umbrella_MD?
>> 
> 
> What would you restrain?  Don't fall into the trap that many people seem to do (despite me warning against it...) and try to follow the tutorial too literally.  Restraining the peptide in the tutorial had a specific purpose.  it's something that probably 99% of umbrella sampling simulations should NOT use.
> 
> Your structure is basically just falling apart.  You may need some inter-peptide restraints to preserve the geometry, but then deconvoluting all of that into a meaningful PMF for just pulling the aggregate through the membrane becomes very challenging.
> 
> -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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