[gmx-users] Umbrella Pulling

Justin A. Lemkul jalemkul at vt.edu
Fri Feb 17 15:12:04 CET 2012



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

> 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://www.bevanlab.biochem.__vt.edu/Pages/Personal/justin
>                     <http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>>
> 
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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://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>
> 
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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

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