[gmx-users] ligand moving out during umbrella sampling
abhisek Mondal
abhisek.mndl at gmail.com
Mon May 8 16:00:34 CEST 2017
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:
>
>> Hi,
>>
>> 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.
>> https://drive.google.com/drive/folders/0B6O-L5Y7BiGJQ1FIc2tIRFE2dE0
>>
>> 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 along
> z, so the ligand can move freely along x and y. 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.
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.
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?
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 ? The
fact that I'm struggling with is to restrain the pull configurations for
further sampling.
I'm really a beginner, so maybe I'm asking stupid questions. Please give me
some advise. I'm really unable to decipher the scenario in comparison to
your amyloid article in JPCB.
You're following the tutorial too literally and that's not correct. Also
> do not restrain the protein (I say this weekly; not enough people are
> reading the details of the tutorial and associated paper and just copying
> .mdp settings...)
>
> -Justin
>
>
>> On Sun, May 7, 2017 at 9:57 AM, abhisek Mondal <abhisek.mndl at gmail.com>
>> wrote:
>>
>> Hi,
>>>
>>> I have completed pulling as per the tutorial stated. But having a strange
>>> issue during umbrella sampling. When I execute:
>>> *mpirun -np 320 /app/gromacs462/bin/mdrun_mpi -v -deffnm umbrella8 -pf
>>> pullf-umbrella8.xvg -px pullx-umbrella8.xvg*
>>>
>>> The gro file generated at the end shows the ligand is way far compared to
>>> starting position, as if another pulling is done !
>>> Please suggest me a way to tackle this issue. If this thing happens to
>>> all
>>> the configurations generated during pulling then how am I supposed to get
>>> the PMF ?
>>>
>>> The md_umbrella.mdp I'm using is:
>>> title = Umbrella pulling simulation
>>> define = -DPOSRES
>>> ; Run parameters
>>> integrator = md
>>> dt = 0.002
>>> tinit = 0
>>> nsteps = 5000000 ; 10 ns
>>> nstcomm = 10
>>> ; Output parameters
>>> nstxout = 50000 ; every 100 ps
>>> nstvout = 50000
>>> nstfout = 5000
>>> nstxtcout = 5000 ; every 10 ps
>>> nstenergy = 5000
>>> ; Bond parameters
>>> constraint_algorithm = lincs
>>> constraints = all-bonds
>>> continuation = yes
>>> ; Single-range cutoff scheme
>>> nstlist = 5
>>> ns_type = grid
>>> rlist = 1.4
>>> rcoulomb = 1.4
>>> rvdw = 1.4
>>> ; PME electrostatics parameters
>>> coulombtype = PME
>>> fourierspacing = 0.12
>>> fourier_nx = 0
>>> fourier_ny = 0
>>> fourier_nz = 0
>>> pme_order = 4
>>> ewald_rtol = 1e-5
>>> optimize_fft = yes
>>> ; Berendsen temperature coupling is on in two groups
>>> Tcoupl = Nose-Hoover
>>> tc_grps = Protein Non-Protein
>>> tau_t = 0.5 0.5
>>> ref_t = 310 310
>>> ; Pressure coupling is on
>>> Pcoupl = Parrinello-Rahman
>>> pcoupltype = isotropic
>>> tau_p = 1.0
>>> compressibility = 4.5e-5
>>> ref_p = 1.0
>>> refcoord_scaling = com
>>> ; Generate velocities is off
>>> gen_vel = no
>>> ; Periodic boundary conditions are on in all directions
>>> pbc = xyz
>>> ; Long-range dispersion correction
>>> DispCorr = EnerPres
>>> ; Pull code
>>> pull = umbrella
>>> pull_ngroups = 1
>>> pull_group0 = Protein_chain_A
>>> pull_group1 = ACO
>>> pull_geometry = direction
>>> pull_dim = N N Y ; pulling in Z dimension
>>> 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
>>>
>>> My question is despite the pull_rate1 being 0.0, why the ligand is moving
>>> ? Is it the pull_start or something else I'm missing here resulting in
>>> such
>>> a crash ?
>>>
>>> Your suggestions will be highly appreciated.
>>> Thank you.
>>>
>>> --
>>> Abhisek Mondal
>>>
>>> *Senior Research Fellow*
>>>
>>> *Structural Biology and Bioinformatics Division*
>>> *CSIR-Indian Institute of Chemical Biology*
>>>
>>> *Kolkata 700032*
>>>
>>> *INDIA*
>>>
>>>
>>
>>
>>
> --
> ==================================================
>
> 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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