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

Justin Lemkul jalemkul at vt.edu
Mon Sep 19 21:33:14 CEST 2016

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 



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


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