[gmx-users] Docked ligand, umbrella sampling and "aiming"

[Justin Lemkul]

On 3/6/15 2:04 AM, Jernej Zidar wrote:
> Hi there,
>    I have a receptor with a docked ligand. I would like to perform an
> umbrella sampling simulation to get some insights into the
> thermodynamics of the binding.
>
>    Following the Umbrella Sampling tutorial I performed the 500 ps
> pulling simulation. A visual examination of the trajectory revealed
> there's an expected change in the position of the ligand that is
> coincidental with a worryingly big increase in the force exerted on
> the ligand. Link to a figure:
> https://www.dropbox.com/s/fj3daaagimuynni/rec-lig-pos-for.pdf?dl=0
>
>    Is this an expected behaviour or should I try to somehow adjust the
> direction of the pulling? If so, could you advise on a strategy to do
> so?
>

This is expected.  You're pulling on a spring at constant velocity, so the force 
on the spring increases with increasing displacement.  It is being resisted by 
the interactions between the pulled group and the reference group.  So the 
applied force is trying to overcome restoring forces in the system.  At some 
point, they break, the pulled group has a net displacement, and the force on the 
spring drops off.

-Justin

-- 
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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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