[gmx-users] ligand moving out during umbrella sampling

[Justin Lemkul]

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

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