[gmx-users] ligand moving out during umbrella sampling
abhisek.mndl at gmail.com
Thu May 11 15:21:22 CEST 2017
On Thu, May 11, 2017 at 11:02 AM, abhisek Mondal <abhisek.mndl at gmail.com>
> 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
> 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
> 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.
> I have choose my reaction coordinate to be along -Z axis and want to apply
> biasing potential accordingly with restraining the ligand movement. Can you
> please suggest where am I failing with this code ?
> Thank you.
> On Tue, May 9, 2017 at 1:11 AM, Justin Lemkul <jalemkul at vt.edu> wrote:
>> On 5/8/17 10:00 AM, abhisek Mondal wrote:
>>> On Sun, May 7, 2017 at 11:37 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>> On 5/7/17 1:57 AM, abhisek Mondal wrote:
>>>>> For your ease of understanding regarding what is happening during this
>>>>> above said umbrella-mdrun, I have shared the trajectory video file the
>>>>> following link.
>>>>> Is this normal given that the mdp code being used ? I basically have no
>>>>> idea with this step, so please help me out. I'm using gromacs-4.6.2.
>>>>> Your setup is incorrect. You're applying a biasing potential only
>>>> z, so the ligand can move freely along x and y. A protein-ligand
>>>> has spherical symmetry, so you should set the reaction coordinate to the
>>>> vector connecting the ligand with some suitable subset of interacting
>>>> protein residues.
>>> I don't get it.
>>> We are trying not to move our configuration (generated after pulling
>>> simulation) along the reaction coordinate, so for restraining we are
>>> supposed to set pull_rate1=0.0.
>> Of course. But you said set pull_k = 0 which does not make sense. The
>> pulling rate *is* zero during umbrella sampling (no net displacement,
>> restrain to the specified distance along the reaction coordinate) and
>> pulling force constant should be non-zero.
>> If applying biasing potential only along z is causing movement along x and
>>> y then what if we apply the biasing potential along x,y,z ? Will it cause
>>> any good in restraining the ligand?
>> This is how it should be done. The reaction coordinate should be
>> suitably defined based on the geometry of the system. As I suggested
>> before, choose some representative residues in the active site as one group
>> and the ligand as the other. Thus defines the reaction coordinate without
>> any presupposition of anything being aligned with a Cartesian axis, which
>> is rarely the case.
>> Moreover, you said previously "A protein-ligand complex has spherical
>>> symmetry, so you should set the reaction coordinate to the vector
>>> connecting the ligand with some suitable subset of interacting protein
>>> residues.". It is really unclear to me, could you please give me some
>>> examples to understand it more simply? I had pulled the ligand along -z
>>> axis, doesn't it mean that the reaction coordinate is to be that way ?
>>> fact that I'm struggling with is to restrain the pull configurations for
>>> further sampling.
>> The reaction coordinate is whatever you define it to be. Whether or not
>> pulling along the z-axis makes sense depends on the orientation of the
>> system and the intrinsic geometry. In your case, it doesn't make sense.
>> In my case (the tutorial, the unidirectional growth of an amyloid fibril)
>> it does make sense to use a single Cartesian axis for the SMD portion and
>> subsequent umbrella sampling.
>> I'm really a beginner, so maybe I'm asking stupid questions. Please give
>>> some advise. I'm really unable to decipher the scenario in comparison to
>>> your amyloid article in JPCB.
>> You should read the article to understand why I did what I did in the
>> tutorial, and then move on to reading articles that are more similar to
>> your case. These will be much more relevant to what you're doing.
>> 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
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> Abhisek Mondal
> *Senior Research Fellow*
> *Structural Biology and Bioinformatics Division*
> *CSIR-Indian Institute of Chemical Biology*
> *Kolkata 700032*
*Senior Research Fellow*
*Structural Biology and Bioinformatics Division*
*CSIR-Indian Institute of Chemical Biology*
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