[gmx-users] Umbrella Pulling

Steven Neumann s.neumann08 at gmail.com
Fri Feb 17 15:45:56 CET 2012


On Fri, Feb 17, 2012 at 2:12 PM, Justin A. Lemkul <jalemkul at vt.edu> wrote:

>
>
> Steven Neumann wrote:
>
>> Hello Justin,
>>
>> As you recommended I run longer pulling of my ligand. I pull the ligand
>> which is on the top of my protein so the top of the protein is pulled so
>> that the whole protein rotated app. 30 degrees - the low part of the
>> protein came out of the box due to the rotation. After app 600 ps the
>> ligand does not move any more and the force applied increase linearly. As I
>> saw the trajectory, ligand does not collide with a periodic image but it
>> does not move. Please, see attacheg plot force vs time. Can you explain why
>> the force increase linearly and ligand is not pulled any more? This is my
>> mdp file for pulling:
>>
>>
> Is the pulled distance greater than half of the box vector in z?  That's
> the only reason I can see things going haywire.  With simple "distance"
> geometry, there are some limitations like that.  Rotation itself is not a
> problem.  You're separating two objects; there's no clear orientation
> dependence in that case.
>
> -Justin
>


As you can see the pulling distance is 5 nm. The lenght of my box in Z
direction is 12 nm. Thus, it is not. Any other ideas?

>
>  title       = Umbrella pulling simulation
>> ; Run parameters
>> integrator  = md
>> dt          = 0.002
>> tinit       = 0
>> nsteps      = 500000    ; 500 ps
>> nstcomm     = 10
>> ; Output parameters
>> nstxout     = 5000      ; every 10 ps
>> nstvout     = 5000
>> nstfout     = 500
>> nstxtcout   = 500       ; every 1 ps
>> nstenergy   = 500
>> ; Bond parameters
>> constraint_algorithm    = lincs
>> constraints             = all-bonds
>> continuation            = yes       ; continuing from NPT
>> ; Single-range cutoff scheme
>> nstlist     = 5
>> ns_type     = grid
>> rlist       = 0.9
>> rcoulomb    = 0.9
>> rvdw        = 0.9
>> ; 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
>> ; Temperature coupling is on
>> tcoupl      = V-rescale                     ; modified Berendsen
>> thermostat
>> tc_grps     = Protein_LIG Water_and_ions   ; two coupling groups - more
>> accurate
>> tau_t       = 0.1   0.1                     ; time constant, in ps
>> ref_t       = 298   298                     ; reference temperature, one
>> for each group, in K
>> ; Pressure coupling is on
>> Pcoupl          = Parrinello-Rahman
>> pcoupltype      = isotropic
>> tau_p           = 1.0      compressibility = 4.5e-5
>> ref_p           = 1.0
>> ; 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_geometry   = distance  ; simple distance increase
>> pull_dim        = N N Y
>> pull_start      = yes       ; define initial COM distance > 0
>> pull_ngroups    = 1
>> pull_group0     = Protein
>> pull_group1     = LIG182
>> pull_rate1      = 0.01      ; 0.01 nm per ps = 10 nm per ns
>> pull_k1         = 200      ; kJ mol^-1 nm^-2
>>
>> Would you recommend position restrained of the protein backbone atoms or
>> e.g. residues from the lower part so that the protien will not roatate?
>>
>> Thank you,
>>
>> Steven
>>
>>
>>
>>
>>
>>
>>
>>    On Fri, Feb 17, 2012 at 10:41 AM, Steven Neumann
>>    <s.neumann08 at gmail.com <mailto:s.neumann08 at gmail.com>**> wrote:
>>
>>
>>
>>
>>
>>        On Mon, Feb 13, 2012 at 2:53 PM, Steven Neumann
>>        <s.neumann08 at gmail.com <mailto:s.neumann08 at gmail.com>**> wrote:
>>
>>            Thank you Justin!
>>
>>
>>            On Mon, Feb 13, 2012 at 2:44 PM, Justin A. Lemkul
>>            <jalemkul at vt.edu <mailto:jalemkul at vt.edu>> wrote:
>>
>>
>>
>>                Steven Neumann wrote:
>>
>>                    Thank you Justin. I run my pulling using two force
>>                    constant for pulling. K1=100 and K1=200
>>                    Please, see attached plots of force vs time. Is
>>                    there any criteria to adjust pulling constant? Would
>>                    you suggest running it for a longer time?
>>
>>
>>                I know of no systematic study for choosing a force
>>                constant.  Guessing wildly at what's going on, I'd say
>>                you need longer simulations as it appears you have only
>>                just caused dissociation towards the end of the 500 ps.
>>
>>                -Justin
>>
>>                    Steven
>>
>>                    On Mon, Feb 13, 2012 at 1:11 PM, Justin A. Lemkul
>>                    <jalemkul at vt.edu <mailto:jalemkul at vt.edu>
>>                    <mailto:jalemkul at vt.edu <mailto:jalemkul at vt.edu>>>
>>
>>                    wrote:
>>
>>
>>
>>                       Steven Neumann wrote:
>>
>>                           Dear Gmx Users,
>>                            Is it always required to restrained
>>                    positions of the protein
>>                           while pulling your ligand? My system is made
>>                    of 10 ligands
>>                           attached to my protein surface. I am pulling
>>                    one of them.
>>
>>
>>                       No, it is not required.  I assume you've gotten
>>                    this idea from my
>>                       tutorial - the restraints there were used for a
>>                    very specific
>>                       purpose (detailed in the paper linked from the
>>                    tutorial).
>>
>>
>>                           I have just seen trajectory of pulling my
>>                    ligand without
>>                           restraining positions of protein and 9
>>                    remaining ligands. My
>>                           ligand while pulling also pulled the protein
>>                    with itself (for 1
>>                           nm distance) and then splited. Is is this
>>                    approach more reliable?
>>
>>                       If your goal is umbrella sampling, you need only
>>                    generate a series
>>                       of reasonable starting configurations along a
>>                    defined reaction
>>                       coordinate.  The absolute positions are
>>                    irrelevant; it is the
>>                       relative distance that matters.
>>
>>                       -Justin
>>
>>                       --     ==============================**
>> ____==========
>>
>>
>>
>>                       Justin A. Lemkul
>>                       Ph.D. Candidate
>>                       ICTAS Doctoral Scholar
>>                       MILES-IGERT Trainee
>>                       Department of Biochemistry
>>                       Virginia Tech
>>                       Blacksburg, VA
>>                       jalemkul[at]vt.edu <http://vt.edu/>
>>                    <http://vt.edu/> | (540) 231-9080
>>                    <tel:%28540%29%20231-9080>
>>                       <tel:%28540%29%20231-9080>
>>                       http://www.bevanlab.biochem.
>>                    <http://www.bevanlab.biochem./**>____
>> vt.edu/Pages/Personal/**justin <http://vt.edu/Pages/Personal/justin>
>>                    <http://vt.edu/Pages/Personal/**justin<http://vt.edu/Pages/Personal/justin>
>> >
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>> >>
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>>                    ------------------------------**
>> __----------------------------**--__------------
>>
>>
>>                    ------------------------------**
>> __----------------------------**--__------------
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>>
>>
>>                --                 ==============================**
>> __==========
>>
>>                Justin A. Lemkul
>>                Ph.D. Candidate
>>                ICTAS Doctoral Scholar
>>                MILES-IGERT Trainee
>>                Department of Biochemistry
>>                Virginia Tech
>>                Blacksburg, VA
>>                jalemkul[at]vt.edu <http://vt.edu/> | (540) 231-9080
>>                <tel:%28540%29%20231-9080>
>>                http://www.bevanlab.biochem.__**
>> vt.edu/Pages/Personal/justin <http://vt.edu/Pages/Personal/justin>
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>> ------------------------------**------------------------------**
>> ------------
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>>
> --
> ==============================**==========
>
> Justin A. Lemkul
> Ph.D. Candidate
> ICTAS Doctoral Scholar
> MILES-IGERT Trainee
> Department of Biochemistry
> Virginia Tech
> Blacksburg, VA
> jalemkul[at]vt.edu | (540) 231-9080
> http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin<http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>
>
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