[gmx-users] Umbrella Sampling

[Steven Neumann]

I am do not want to choose different pulling conditions as I build a model
for specific force constant and pulling rate in given force filed. I think
restraining would help much more to then exclude the ions impact.

Steven


On Wed, Jul 31, 2013 at 12:49 PM, Steven Neumann <s.neumann08 at gmail.com>wrote:

> Thank you a lot!
>
>
> On Wed, Jul 31, 2013 at 12:46 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>>
>> 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 <jalemkul at outerbanks.umaryland.edu>| (410)
>> 706-7441
>>
>> ==============================**====================
>>
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>
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