[gmx-users] Unstable Minimizations

Justin A. Lemkul jalemkul at vt.edu
Mon Jan 11 03:58:33 CET 2010



On 1/10/10 9:47 PM, Jack Shultz wrote:
> Thanks Justin,
> I went back to the original pdb files. These were conformations of the
> same protein derived from molecular dynamics simulations performed by
> Andrey.
> What I intially attempted was preping the structures using tleap, hoping
> to paint in missing atoms for residues. Then use this to replace

Well, it seems that you may be hoping for too much :)  Your log file shows a 
whole bunch of failures that look to be related to some early processing of your 
structure, and other warnings about close contacts detected in tleap.

I think you may need to start with an actual intact structure, or else coax your 
preparation steps to make this happen.  I am not too familiar with tleap and 
sleap, do they magically fix missing atoms?

-Justin

> non-standard residues
> sed s/PRO\ A\ \ \ 1/NPROA\ \ \ 1/g fzd2_md7-8_c6_cc.pdb | sed s/PRO\ B\
> \ \ 1/NPROB\ \ \ 1/g | sed s/PHE\ A\ \ 99/CPHEA\ \ 99/g | sed s/PHE\ B\
> \ 99/CPHEB\ \ 99/g | sed s/O\ \ \ CPHE/OC1\ CPHE/g | sed s/OXT\
> CPHE/OC2\ CPHE/g | sed s/HIS\ /HID\ /g | sed s/LYS\ /LYP\ /g | sed
> s/CYS\ /CYN\ /g > protein2.pdb
> Then fixed the nterminal residue name. Finally replaced all CYS to CYS2
> I went back and did the same thing except for tleap. It pdb2gmx seems to
> process these files without needing the tleap step.
> Still I see some of the same lincs errors.
> rms 10.669050, max 173.182678 (between atoms 1857 and 1859)
> rms 10.669803, max 173.177811 (between atoms 1857 and 1859)
> rms 10.670179, max 173.175400 (between atoms 1857 and 1859)
> rms 10.670368, max 173.174149 (between atoms 1857 and 1859)
> rms 10.670460, max 173.173553 (between atoms 1857 and 1859)
> rms 10.670508, max 173.173141 (between atoms 1857 and 1859)
> rms 10.670531, max 173.173035 (between atoms 1857 and 1859)
> rms 10.670543, max 173.172958 (between atoms 1857 and 1859)
> rms 10.670549, max 173.172928 (between atoms 1857 and 1859)
> rms 10.670552, max 173.172913 (between atoms 1857 and 1859)
> rms 10.670554, max 173.172913 (between atoms 1857 and 1859)
> rms 10.670554, max 173.172913 (between atoms 1857 and 1859)
> ATOM   1857  CA  HIE   120      43.362  28.084  25.727  1.00  0.00
> ATOM   1858  HA  HIE   120      43.677  27.135  25.748  1.00  0.00
> ATOM   1859  CB  HIE   120      42.112  28.226  24.788  1.00  0.00
> also this atom consistently has a very high Fmax
> Step=    3, Dmax= 1.4e-02 nm, Epot=  1.45860e+10 Fmax= 2.82224e+12,
> atom= 19392
> Step=    4, Dmax= 7.2e-03 nm, Epot=  1.45396e+10 Fmax= 2.82207e+12,
> atom= 19392
> Step=    5, Dmax= 3.6e-03 nm, Epot=  1.45106e+10 Fmax= 2.82194e+12,
> atom= 19392
> Step=    6, Dmax= 1.8e-03 nm, Epot=  1.44953e+10 Fmax= 2.82181e+12,
> atom= 19392
> Step=    7, Dmax= 9.0e-04 nm, Epot=  1.44887e+10 Fmax= 2.82196e+12,
> atom= 19392
> Step=    8, Dmax= 4.5e-04 nm, Epot=  1.44850e+10 Fmax= 2.82196e+12,
> atom= 19392
> Step=    9, Dmax= 2.2e-04 nm, Epot=  1.44832e+10 Fmax= 2.82196e+12,
> atom= 19392
> Step=   10, Dmax= 1.1e-04 nm, Epot=  1.44822e+10 Fmax= 2.82196e+12,
> atom= 19392
> Step=   11, Dmax= 5.6e-05 nm, Epot=  1.44818e+10 Fmax= 2.82196e+12,
> atom= 19392
> Step=   12, Dmax= 2.8e-05 nm, Epot=  1.44815e+10 Fmax= 2.82196e+12,
> atom= 19392
> Step=   13, Dmax= 1.4e-05 nm, Epot=  1.44814e+10 Fmax= 2.82196e+12,
> atom= 19392
> Its not clear to me what we should do to correct this structures...maybe
> Andrey has some input.
> http://boinc.drugdiscoveryathome.com/em_restrained_rcs_mdrun2.txt
> On Sun, Jan 10, 2010 at 5:37 PM, Justin A. Lemkul <jalemkul at vt.edu
> <mailto:jalemkul at vt.edu>> wrote:
>
>
>
>     On 1/10/10 5:18 PM, Jack Shultz wrote:
>
>         I am trying to get this workflow opperational. However, my
>         systems are
>         getting unstable. I have preped two mdp files: 1) one for
>         restrained 2)
>         unrestrained. LINCS errors appear for restrained and
>         unrestrained has
>         infinite energy appearing.
>         http://boinc.drugdiscoveryathome.com/_em_restrained_rcs_mdrun.txt_
>
>         <http://boinc.drugdiscoveryathome.com/em_restrained_rcs_mdrun.txt>
>         __
>
>
>     This log file shows several "long bond" warnings, which may be the
>     root of your problem.  See here:
>
>     http://www.gromacs.org/Documentation/Errors#Long_bonds_and.2for_missing_atoms
>
>     Since your minimization is failing immediately, there is something
>     physically unreasonable about your structure, such that EM cannot
>     resolve the problem. Note, too, that one of the long bond warnings
>     pertained to atom 1668, which is the location of the first LINCS
>     warning.  Coincidence?  Not likely.  Re-examine the starting
>     structure and figure out if anything is missing or poorly
>     reconstructed (e.g., from initially missing atoms).
>
>
>         This is where I get the LINCS Warnings
>         Step -1, time -0.001 (ps)  LINCS WARNING
>         relative constraint deviation after LINCS:
>         rms 0.461520, max 14.428611 (between atoms 1668 and 1669)
>         bonds that rotated more than 30 degrees:
>         atom 1 atom 2  angle  previous, current, constraint length
>         Steepest Descents:
>             Tolerance (Fmax)   =  1.00000e+04
>             Number of steps    =          100
>         Warning: 1-4 interaction between 1658 and 1672 at distance 2.655
>         which
>         is larger than the 1-4 table size 2.400 nm
>         These are ignored for the rest of the simulation
>         This usually means your system is exploding,
>         if not, you should increase table-extension in your mdp file
>         or with user tables increase the table size
>         Step=    0, Dmax= 1.0e-02 nm, Epot=  1.09364e+09 Fmax= 2.21154e+11,
>         atom= 3292
>         Step 1, time 0.001 (ps)  LINCS WARNING
>         relative constraint deviation after LINCS:
>         rms 0.680509, max 22.293625 (between atoms 1668 and 1670)
>         bonds that rotated more than 30 degrees:
>         atom 1 atom 2  angle  previous, current, constraint length
>         What is a reasonable increase in table-extension. Is this a
>         mis-leading
>         suggestion?
>
>
>     You should not adjust the table-extension.  The other part of the
>     error message is what you need to pay attention to ("your system is
>     exploding").
>
>     -Justin
>
>         Here is the log from the unrestrained minimization.
>         http://boinc.drugdiscoveryathome.com/_em_rcs_mdrun.txt_
>
>         <http://boinc.drugdiscoveryathome.com/em_rcs_mdrun.txt>
>         Here is a zip archive containing the working directory for this
>         minimization. Its about 428 kb
>         http://boinc.drugdiscoveryathome.com/rcs_ga_run_10_bt_Fzd2-MD7-MD8-7.zip_lig_24205_ChemDiv_5754-2873_ts_1263004110202172000.zip
>
>         --
>         Jack
>
>         http://drugdiscoveryathome.com <http://drugdiscoveryathome.com/>
>         http://hydrogenathome.org <http://hydrogenathome.org/>
>
>
>     --
>     ========================================
>
>     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
>     http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>
>     ========================================
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>
>
> --
> Jack
>
> http://drugdiscoveryathome.com
> http://hydrogenathome.org

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

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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