[gmx-users] The Rationality of Position Restrain in Umbrella Sampling

Justin Lemkul jalemkul at vt.edu
Tue May 2 15:56:05 CEST 2017

On 5/2/17 9:54 AM, Jason Zhu wrote:
> Dear All,
> I am modeling the free binding energy between two molecules following the
> Gromacs Tutorial 3: Umbrella Sampling (
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html
> ).
> In this tutorial, the Chain_B of proteins is fixed as an immobile reference
> by position restrain during not only the stage of Steered MD but also the
> stage of Umbrella Sampling.
> I am wondering what the rationality of the position restrain is for the
> calculation of free energy. Does this reduce of degree of freedom due to
> the position restrain have any artificial influence on the calculated free
> energy?

Please read the paper I linked from the tutorial, and references therein, which 
explain this rather unique case.  Normally one does not need additional 
restraints during US.


> Why don't we just use "COM motion removal" method to fix the COM of the
> protein complex and use pulling method to separate the Chain_A from other
> protein chains? Is it because of the excessively strong binding between
> them? If we use position restrain, do we need to make some corrections to
> the calculated binding free energy, just like the below paper?
> Boresch, S., Tettinger, F., Leitgeb, M., and Karplus, M. (2003) Absolute
> binding free energies: A quantitative approach for their calculation. J.
> Phys. Chem. A 107, 9535–9551
> (http://pubs.acs.org/doi/abs/10.1021/jp0217839)
> Best,
> Wenpeng Zhu


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


More information about the gromacs.org_gmx-users mailing list