[gmx-users] Question on Umbrella Sampling with varied ionic strength.

[Justin Lemkul]

On 7/31/17 5:19 PM, Yuanchao Liu (MSU) wrote:
> Hi all
> 
> I have a question on umbrella sampling results under varied ionic strength.
> I have just done some regular umbrella sampling on the system of glucose
> 6-phosphate (small ligand molecule) on oligopeptide with LYS side chains. I
> mostly follow the tutorial by Justin
> <https://urldefense.proofpoint.com/v2/url?u=http-3A__www.bevanlab.biochem.vt.edu_Pages_Personal_justin_gmx-2Dtutorials_umbrella_index.html&d=DwIFaQ&c=nE__W8dFE-shTxStwXtp0A&r=gCy395jfSTIKIGBjdJ8SwSg8yN7wywRqF0ilx8ZoefpMNPZKIUY0jXzHKcFUwcQV&m=wjjoIomb4xozoyp9lqY4_wEzyhxGWILHcyUjAvXhess&s=--TZVWbKNWMqlgnHsfsMQUCzOJsx1PMTs4thX-y0jhM&e= >.
> I use explicit ions to represent the ionic strength level.
> 
> There is hardly any difference between my calculated adsorption energy (by
> PMF) under different ionic strengths (0, 20, 40, 70, 120 mM). However, we
> did observe apparent difference on surface retention time in regular MD
> simulations, which indicated a weaker surface interaction. During my
> simulation, the sampling time is 10 ns for each window, and I am wondering
> if the effect of explicit ions need longer simulation time to be reflected
> on results.
> 
> Here is some detail of my simulation:
> https://urldefense.proofpoint.com/v2/url?u=http-3A__www.evernote.com_l_AAMCVXRkp3tPYrhq-5F4oRHdtfnRb1VJo71U0_&d=DwIFaQ&c=nE__W8dFE-shTxStwXtp0A&r=gCy395jfSTIKIGBjdJ8SwSg8yN7wywRqF0ilx8ZoefpMNPZKIUY0jXzHKcFUwcQV&m=wjjoIomb4xozoyp9lqY4_wEzyhxGWILHcyUjAvXhess&s=B67nP5cwU6r5g_KBORUyrzAardEsfEzcojVKVZFomfU&e=
> 
> I will appreciate it if anybody with relevant experience can give me some
> suggestion on this. Thank you.
> 

It will be difficult to determine any real, meaningful difference with such 
small changes in ionic strength.  Your histogram overlap looks good, so I doubt 
that more sampling will improve the result.  Is the observed difference in 
retention time reproducible?  How did you determine it, and over what time 
scale?  Is it possible that those simulations simply got stuck in a local 
minimum (common in MD simulations) rather than actually reflecting a real 
physical difference?  Additionally, if the retention times are not substantially 
different, then the energy differences may not be large enough to resolve via 
umbrella sampling.

-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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