[gmx-users] MARTINI force-field in pulling simulations

Justin Lemkul jalemkul at vt.edu
Thu Feb 7 13:05:30 CET 2013



On 2/7/13 5:20 AM, Davide Mercadante wrote:
> Dear All,
>
> I am trying to run a pulling simulation on a small protein (18 aa) using
> the GC forcefield MARTINI (v2.2). I have energy minimized and
> equilibrated (NPT) my system and everything seems fine. My system
> consists of the protein + water + ions NA+ and CL-.
>
> After the equilibration I start a constant velocity pulling along the
> z-direction of the last atom of the chain while the first atom is
> positionally restrained in xyz (basically I am stretching the protein).
> At some point from the start of the pulling simulation and before
> reaching the full extension of the chain (force profile is still
> steadily increasing without peaking) the simulation crashes giving me
> these LINCS warnings:
>
> Step 293252, time 5865.04 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.157274, max 0.291135 (between atoms 10 and 11)
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>
> Step 293252, time 5865.04 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.128562, max 0.230219 (between atoms 7 and 8)
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>
> Step 293253, time 5865.06 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.413291, max 0.828515 (between atoms 7 and 8)
>
> Step 293253, time 5865.06 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.587032, max 0.986890 (between atoms 11 and 13)
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>        7      8   46.6    0.2686   0.0579      0.3500
>       10     11  121.3    0.2481   0.0550      0.3500
>       13     15  168.5    0.2851   0.0278      0.3500
>
> Step 293253, time 5865.06 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.108373, max 0.322423 (between atoms 19 and 21)
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>        7      8   45.0    0.2686   0.0600      0.3500
>       10     11   88.1    0.2481   0.0497      0.3500
> Wrote pdb files with previous and current coordinates
> Wrote pdb files with previous and current coordinates
>
> Step 293254, time 5865.08 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.330732, max 0.654588 (between atoms 23 and 25)
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>       21     23   42.0    0.2905   0.1426      0.3500
>       17     18   92.9    0.3146   0.1560      0.3000
>       15     17   35.3    0.5839   0.4003      0.3500
>       13     15  141.6    0.0278   0.2742      0.3500
>
> Step 293254, time 5865.08 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.312540, max 0.555587 (between atoms 19 and 21)
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>        8      9   48.0    0.3406   0.1435      0.3100
>        7      8   82.3    0.0579   0.4596      0.3500
>       10     11  102.9    0.0550   0.5130      0.3500
>       11     12   51.9    0.5425   0.3643      0.4000
>       11     13   38.5    0.6954   0.1898      0.3500
>       13     15  143.4    0.0278   0.2879      0.3500
>       15     17   37.3    0.5839   0.3730      0.3500
>
> Step 293254, time 5865.08 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.343084, max 0.751867 (between atoms 3 and 5)
>       17     18   93.2    0.3146   0.1563      0.3000
>       21     23   41.6    0.2905   0.1443      0.3500
>       23     24   33.0    0.3784   0.4007      0.4000
>       11     13   58.2    0.6954   0.3283      0.3500
>       23     24   33.1    0.3784   0.3999      0.4000
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>        7      8   82.2    0.0579   0.4605      0.3500
>        8      9   48.4    0.3406   0.1439      0.3100
>       10     11  104.0    0.0550   0.5496      0.3500
>       11     12   57.6    0.5425   0.3679      0.4000
>       11     13   61.9    0.6954   0.1402      0.3500
>       13     15  141.2    0.0278   0.4588      0.3500
> Wrote pdb files with previous and current coordinates
> Wrote pdb files with previous and current coordinates
> Wrote pdb files with previous and current coordinates
>
> Step 293255, time 5865.1 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 32.745333, max 105.228383 (between atoms 17 and 18)
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>        5      6   30.3    0.3950   0.3971      0.4000
>       13     15  172.9    0.2879   4.6287      0.3500
>       15     16   33.0    0.2435   5.0674      0.3300
>       15     17   51.2    0.3730  11.1793      0.3500
>       17     18  107.1    0.1563  31.8685      0.3000
>       17     19  143.4    0.3380  10.1576      0.3500
>       19     20   86.5    0.3397   6.2047      0.3300
>       21     22  103.7    0.3750   6.6220      0.4000
>       21     23  150.3    0.1426   6.8152      0.3500
>
> Step 293255, time 5865.1 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 10.273318, max 30.025748 (between atoms 19 and 21)
>       23     24  149.4    0.3999   1.3487      0.4000
>       25     26   79.9    0.3039   2.4910      0.3000
>       25     27  165.9    0.2225   2.4307      0.3500
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>       21     22  103.7    0.3750   6.6180      0.4000
>       21     23  150.2    0.1426   6.8083      0.3500
>       19     20   86.5    0.3397   6.2048      0.3300
>       17     19  143.4    0.3380  10.1586      0.3500
>       17     18  107.1    0.1563  31.8685      0.3000
>       15     17   51.2    0.3730  11.1771      0.3500
>       15     16   33.0    0.2435   5.0657      0.3300
>       13     15  173.1    0.2879   4.6383      0.3500
>       23     24  149.5    0.3999   1.3474      0.4000
>       25     26   79.9    0.3039   2.4804      0.3000
>       25     27  165.7    0.2225   2.3691      0.3500
>       28     29   44.1    0.3191   0.0921      0.3100
>       28     30   39.4    0.3101   0.2122      0.3500
> Wrote pdb files with previous and current coordinates
> Wrote pdb files with previous and current coordinates
>
> Step 293256  Warning: pressure scaling more than 1%, mu: 2.21304 2.21304
> 2.21304
>
> Step 293256  Warning: pressure scaling more than 1%, mu: 2.21304 2.21304
> 2.21304
>
> Step 293256  Warning: pressure scaling more than 1%, mu: 2.21304 2.21304
> 2.21304
>
> Step 293256  Warning: pressure scaling more than 1%, mu: 2.21304 2.21304
> 2.21304
>
> Step 293256  Warning: pressure scaling more than 1%, mu: 2.21304 2.21304
> 2.21304
>
> Step 293256  Warning: pressure scaling more than 1%, mu: 2.21304 2.21304
> 2.21304
>
> Step 293256  Warning: pressure scaling more than 1%, mu: 2.21304 2.21304
> 2.21304
>
> Step 293256  Warning: pressure scaling more than 1%, mu: 2.21304 2.21304
> 2.21304
>
> Step 293256, time 5865.12 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 3192.715629, max 6000.654094 (between atoms 25 and 26)
>
> Step 293256, time 5865.12 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 0.212149, max 0.517573 (between atoms 5 and 7)
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>        5      7   37.9    0.3543   0.5312      0.3500
>        7      8   33.5    0.3821   0.3834      0.3500
>        8      9   56.8    0.3361   0.3502      0.3100
>        8     10  165.7    0.3548   1.0526      0.3500
>
> Step 293256, time 5865.12 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> rms 95.799929, max 246.403254 (between atoms 19 and 21)
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>        8      9   56.7    0.3361   0.3566      0.3100
>        8     10  165.7    0.3548   1.0708      0.3500
>        7      8   33.4    0.3821   0.3897      0.3500
>        5      7   37.9    0.3543   0.5312      0.3500
>       11     12  121.6    0.2312   2.6433      0.4000
>       11     13  149.8    0.3060  15.6610      0.3500
>       13     14  123.6    0.4129  14.6116      0.4000
>       13     14  124.2    0.4129  14.9085      0.4000
>       13     15  169.6    4.6287  44.1184      0.3500
>       11     12  121.1    0.2312   2.7328      0.4000
>       11     13  149.6    0.3060  15.9678      0.3500
>       15     16  168.1    5.0674  39.6694      0.3300
>       15     17  159.6   11.1793  63.3062      0.3500
>       17     18  114.1   31.8685  33.0371      0.3000
>       17     19  112.0   10.1576  36.5026      0.3500
>       19     20   71.0    6.2047   9.2619      0.3300
>       23     24   62.3    1.3474 352.2061      0.4000
>       25     26   63.9    2.4804 1800.5086      0.3000
>       25     27   67.1    2.3691 2007.2339      0.3500
>       13     15  169.4    4.6287  43.0156      0.3500
>       27     28   66.0    0.6878 1992.3756      0.3500
> bonds that rotated more than 30 degrees:
>   atom 1 atom 2  angle  previous, current, constraint length
>       19     20   71.0    6.2047   9.2610      0.3300
>       17     19  112.0   10.1576  36.4983      0.3500
>       17     18  114.1   31.8685  33.0303      0.3000
>       15     17  159.6   11.1793  63.3215      0.3500
>       15     16  168.1    5.0674  39.6801      0.3300
>       13     15  169.6    4.6287  44.0779      0.3500
>       13     14  124.6    0.4129  14.7983      0.4000
>       11     13  148.8    0.3060  16.1472      0.3500
>       23     24   62.3    1.3474 352.1905      0.4000
>       25     26   63.9    2.4804 1800.4962      0.3000
>       25     27   67.1    2.3691 2007.1944      0.3500
>       27     28   66.0    0.6878 1992.3052      0.3500
>       28     29   44.6    0.0921 600.7400      0.3100
>       28     30  137.0    0.2122 696.2760      0.3500
>       30     31   38.7    0.2803 155.6825      0.2650
> Wrote pdb files with previous and current coordinates
> Wrote pdb files with previous and current coordinates
>
> I have a feeling that this happens when I am reaching the full extension
> of the chain because if in the input file (pull.mdp - copied below) I
> increase the pull rate the simulation simply crashes before.
> This crash does not happen in a full-atom simulation of the same protein
> (using for example OPLS) and the force profile reaches the peak wanted
> when the protein approaches the full extension.
>
> I was wondering if you please could help me to understand why this
> happens, if this is a force-field related issue and how I could possibly
> solve the problem.
> The force costant I apply in the posre.itp file for atom number 1 is
> 5000 kj mol^1 nm^2 while the pulling force constant (harmonic potential)
> is 500 kj mol^1 nm^2.
> The pull.mdp input file is appended below.
>
> title       = Umbrella pulling simulation
> define      = -DPOSRES
> ; Run parameters
> integrator  = md
> dt          = 0.02
> tinit       = 0
> nsteps      = 500000   ; 10000.00 ps
> nstcomm     = 10
> ; Output parameters
> nstxout     = 100      ; every 2 ps
> nstvout     = 100
> nstfout     = 100
> nstxtcout   = 100       ; every 2 ps
> nstenergy   = 100
> ; Bond parameters
> constraint_algorithm    = lincs
> constraints             = all-bonds
> continuation            = yes       ; continuing from NPT
> ; 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      = V-rescale
> tc_grps     = Protein   Non-Protein
> tau_t       = 2         2
> ref_t       = 310       310
> ; Pressure coupling is on
> Pcoupl          = Berendsen
> pcoupltype      = isotropic
> tau_p           = 2.0
> 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_geometry = direction
> pull_start = yes  ; (we don't want to calculate the initial distance
> between 'pull' and 'freeze' by hand)
> pull_ngroups = 1  ; (because the reference group doesn't count to this
> value)
> pull_dim = N N Y  ; (because we want to pull only along the z-axis)
> pull_group0 = freeze
> pull_group1 = pull
> pull_vec1 = 0 0 1
> pull_init1 = 0.0 0.0 0.0
> pull_rate1 = 0.001
> pull_k1    = 500
> pull_constr_tol = 1e-6
> pull_pbc_atom0 = 0
> pull_kB1 = 500
> pull_nstxout = 100 ; every 2 ps
> pull_nstfout = 100 ; every 2 ps
>
> Thank you, any suggestions will be greatly appreciated.

Try reducing the time step.

-Justin

-- 
========================================

Justin A. Lemkul, Ph.D.
Research Scientist
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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