[gmx-users] Umbrella Sampling

[Justin Lemkul]

On 7/31/13 6:52 AM, Steven Neumann wrote:
> But even though on the other hand that could be more realistic free energy
> which could be compare to experiment which also involves ions. Would Justin
> please comment on this?
>

I can offer you nothing more than a hand-waving explanation of what I think 
might happen here, so take that for what it's worth.  Since you explicitly asked 
for my thoughts, such as they are...

The dissociation of the ions may be nothing more than an artifact of the pulling 
conditions.  Have you tried different force constants and pull rates to see if 
this behavior is affected?

>
> On Wed, Jul 31, 2013 at 11:46 AM, Steven Neumann <s.neumann08 at gmail.com>wrote:
>
>> They do not dissociate...Are you sure? My mdp specifies only ligand as a
>> pull_group1. I think it would change having ions in this group included.
>>

Even though you're not explicitly pulling the ions, they are being forced to 
move due to the biasing potential that you are applying.

I would think that sufficient sampling in each window (i.e. enough time that you 
might see dissociation of the ions) would provide you with enough information, 
but that's hard to predict.  My assumption would be that the ions will 
absolutely impact the free energy of binding, but from what you said above, 
maybe that's right.  Maybe it's not.  Only way to find out would be to either 
exclude the ions or otherwise restrain their initial positions so that you get a 
"clean" reaction coordinate involving only the ligand.  Then you can decompose 
the different contributions to the free energy of binding.

-Justin

>>
>> On Wed, Jul 31, 2013 at 11:01 AM, lloyd riggs <lloyd.riggs at gmx.ch> wrote:
>>
>>>
>>>> will get the PMF profile for my
>>>> ligand binding or ligand and two ions binding?
>>>
>>> It would be the ligand and two ions unless the ions also at some point
>>> discossiate from the ligand once in solvent. Could add positional restraint
>>> for them, but dont know how that effects the calculation?
>>>   *Gesendet:* Mittwoch, 31. Juli 2013 um 09:29 Uhr
>>> *Von:* "Steven Neumann" <s.neumann08 at gmail.com>
>>> *An:* "Discussion list for GROMACS users" <gmx-users at gromacs.org>
>>> *Betreff:* [gmx-users] Umbrella Sampling
>>> Dear Gmx Users,
>>>
>>> I run SMD to extract the windows for US calculations. The system involves
>>> negatively charged ligand and protein. I generated the protein-ligand
>>> complex within self assembly MD simulations.
>>>
>>> I pulled my molecule away and two ions were also detached from the protein
>>> surface being attached to my ligand.
>>>
>>> My question: if I run my US caluclation and combine windows by WHAM (I
>>> specified in my umbrella.mdp my ligand as a pull_group1 and same protein
>>> residues I pulled it from as pull_group0) will get the PMF profile for my
>>> ligand binding or ligand and two ions binding?
>>>
>>> Steven
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>>
>>

-- 
==================================================

Justin A. Lemkul, Ph.D.
Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 601
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441

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