[gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

On 5/7/17 2:22 PM, abhisek Mondal wrote:
> Hello Justin,
> Thank you for the explanation. I'm really new to the field so choosing
> factors in a bit confusion.
>
> You said in this set up the ligand can still move around X and Y direction.
> My question is what if I set pull_k1=0? The ligand also won't move this
> way.

If you set pull_k1 to zero, it won't accomplish anything at all.  You'll have no 
biasing force.

> You mentioned that during this run we want to restrain the ligand or don't
> want to change the configuration generated by pulling simulation.
> Is this approach right?
>

I don't understand the second question.

-Justin

>
>
> On May 7, 2017 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.  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

==================================================