[gmx-users] ligand moving out during umbrella sampling
abhisek Mondal
abhisek.mndl at gmail.com
Wed May 17 14:55:11 CEST 2017
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.
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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--
Abhisek Mondal
*Senior Research Fellow*
*Structural Biology and Bioinformatics Division*
*CSIR-Indian Institute of Chemical Biology*
*Kolkata 700032*
*INDIA*
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