[gmx-users] Unstable Minimizations

Jack Shultz js at drugdiscoveryathome.com
Mon Jan 11 17:50:32 CET 2010 

Well some of the problems in the log relate to unresolved exceptions
processing the ligands, those ligands are skipped. But I should probably
just test the receptors seperate from the workflow and merged ligands. I
will check this list provided by Tsjerk. Possibly the numbering is off.
Anyway its the structures that need a little work.
6. there should be no atoms in residues that are not listed in the
building block entry, except possibly for hydrogen atoms, which can be
stripped using the -ignh flag
Currently I use -ignh, should I see what happens when I remove this option?
Will that reveal innappropriate atoms that I should remove?
On Sun, Jan 10, 2010 at 9:58 PM, Justin A. Lemkul <jalemkul at vt.edu> wrote:

>
>
> 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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-- 
Jack

http://drugdiscoveryathome.com
http://hydrogenathome.org
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