[gmx-users] ligand moving out during umbrella sampling
Justin Lemkul
jalemkul at vt.edu
Thu May 18 15:18:20 CEST 2017
On 5/17/17 8:55 AM, abhisek Mondal wrote:
> This time I think I got ligand restrained successfully during the umbrella
> sampling. I have removed the restrain from protein, as per your advice.
> Defined the COM vector in md_umbrella.mdp, applied pull_k1=1000 and used
> pull_rate1=0.0.
> I have uploaded the trajectory movie (and other mdp files) in the following
> link:
> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>
> However, I'm facing a problem. Due to the withdrawal of the position
> restrain of protein. The protein and ligand (together) is moving around the
> box and resulting in "Distance of pull group 1 (10.441990 nm) is larger
> than 0.49 times the box size (10.646989)" error.
>
> As per the video I have uploaded, if I assume this approach worked, then
> how can I avoid this error ? Is there any way to make sure the
> protein-ligand remains in the middle of the box (or nearby). I have taken
> pretty large box compared to the protein structure from the beginning.
>
> Please suggest me a way out.
>
Use a larger box or use direction-periodic geometry.
-Justin
> On Mon, May 15, 2017 at 5:48 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>>
>> On 5/15/17 2:45 AM, abhisek Mondal wrote:
>>
>>> On Thu, May 11, 2017 at 9:03 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>
>>>
>>>>
>>>> On 5/11/17 9:21 AM, abhisek Mondal wrote:
>>>>
>>>> On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal <abhisek.mndl at gmail.com
>>>>>>
>>>>> wrote:
>>>>>
>>>>> Hi,
>>>>>
>>>>>>
>>>>>> Thank you for the explanation. It really cleared some concepts. But I'm
>>>>>> still having my ligand moving in this step. I have modified the code
>>>>>> as:
>>>>>> ; Pull code
>>>>>> pull = umbrella
>>>>>> pull_ngroups = 1
>>>>>> pull_group0 = Protein_chain_A
>>>>>> pull_group1 = ACO
>>>>>> pull_geometry = direction ; simple distance increase
>>>>>> pull_dim = Y Y Y ; not to allow ligand move along
>>>>>> other
>>>>>> dir
>>>>>> pull_rate1 = 0.0
>>>>>> pull_k1 = 1000 ; kJ mol^-1 nm^-2
>>>>>> pull_start = yes ; define initial COM distance > 0
>>>>>> pull_vec1 = 0 0 -1
>>>>>>
>>>>>>
>>>>>> Note that with "direction" geometry, only pull_vec1 is acting.
>>>> pull_dim
>>>> is ignored.
>>>>
>>>> The ligand was previously moving along x,y direction when I was using
>>>>
>>>>> pull_dim = N N Y. So I changed it to Y in all direction and provided 0
>>>>>> as
>>>>>> vector and pull_rate1=0.0, so that it does not move much. But at the
>>>>>> end
>>>>>> of a 10ns run, I see that the ligand is still moving as it was earlier.
>>>>>>
>>>>>> It shows me:
>>>>>>
>>>>> Pull group natoms pbc atom distance at start reference at t=0
>>>>> 0 1132 936665
>>>>> 1 59 1618 -1.555 -1.555
>>>>> Is it ok withe negative value ? Anyway this setup is not working.
>>>>>
>>>>>
>>>>> Again you're trying to just apply the restraint to one dimension and it
>>>> looks to be fairly arbitrary. I already suggested using the vector
>>>> connecting the ligand COM with the binding site residues' COM and using
>>>> that as pull_vec1. Draw it out. It makes a lot more sense than trying
>>>> to
>>>> restrain only along one axis, which as I have said before, makes no sense
>>>> in this case.
>>>>
>>>> Thank you for such detailed suggestion.
>>>>
>>> I followed on as per your suggestion. Calculated COM of protein and
>>> Ligand.
>>> Calculated protein-lig vector (using COM) to be used for pulling (as
>>> pull_vec1).
>>> Pulling also achieved successfully.
>>> But after pulling, when I performed the brief npt_umbrella run with
>>> pull_rate1=0, I found the ligand is moving little bit. Could not
>>> understand
>>> what I have mistaken this time.
>>> So I moved on for umbrella sampling mdrun step, with pull_rate1=0 and
>>> pull_vec1=as determined from COM calculations. Despite I found that the
>>> ligand is moving vigorously and got pulled away probably.
>>> I'm putting npt_umbrella.mdp,md_umbrella.mdp,conf140.gro(used for
>>> npt_umbrella), npt140.gro,md_umbrella run video in the following link:
>>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>>
>>>
>>> Am I still missing some drastic steps ? Please suggest me if I do. I'm
>>> totally lost here in this regard.
>>>
>>>
>> Again, don't restrain the protein. I've said this multiple times.
>>
>> The pull setup looks reasonable. Maybe you just need a stronger force
>> constant, or you should not use the COM of the whole protein, instead the
>> COM of a few important residues (use an index group with gmx traj -ox -com
>> to get its coordinates). If the specified vector is off, so too will be
>> the resulting biasing potential.
>>
>> -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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>
>
>
--
==================================================
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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