[gmx-users] Unstable Minimizations

Justin A. Lemkul jalemkul at vt.edu
Mon Jan 11 17:57:44 CET 2010



Jack Shultz wrote:
> 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?

Removing -ignh implies that all hydrogen atoms are present and named according 
to the specifics of the building blocks.  It's not a useful diagnostic for 
missing or "inappropriate" atoms.  What is of great concern (as Tsjerk pointed 
out) is the 3-nm bond identified by pdb2gmx.  Is there a missing loop in the 
protein?

-Justin

> On Sun, Jan 10, 2010 at 9:58 PM, Justin A. Lemkul <jalemkul at vt.edu 
> <mailto: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>
>         <mailto: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://drugdiscoveryathome.com/>
>                http://hydrogenathome.org <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/> <http://vt.edu/> | (540)
>         231-9080
> 
>            http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> 
>            ========================================
>            --
>            gmx-users mailing list gmx-users at gromacs.org
>         <mailto:gmx-users at gromacs.org>
>            <mailto:gmx-users at gromacs.org <mailto:gmx-users at gromacs.org>>
> 
>            http://lists.gromacs.org/mailman/listinfo/gmx-users
>            Please search the archive at http://www.gromacs.org/search before
>            posting!
>            Please don't post (un)subscribe requests to the list. Use the www
>            interface or send it to gmx-users-request at gromacs.org
>         <mailto:gmx-users-request at gromacs.org>
>            <mailto:gmx-users-request at gromacs.org
>         <mailto:gmx-users-request at gromacs.org>>.
> 
>            Can't post? Read http://www.gromacs.org/mailing_lists/users.php
> 
> 
> 
> 
>         --
>         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
> 
>     ========================================
>     -- 
>     gmx-users mailing list    gmx-users at gromacs.org
>     <mailto:gmx-users at gromacs.org>
>     http://lists.gromacs.org/mailman/listinfo/gmx-users
>     Please search the archive at http://www.gromacs.org/search before
>     posting!
>     Please don't post (un)subscribe requests to the list. Use the www
>     interface or send it to gmx-users-request at gromacs.org
>     <mailto:gmx-users-request at gromacs.org>.
>     Can't post? Read http://www.gromacs.org/mailing_lists/users.php
> 
> 
> 
> 
> -- 
> 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

========================================



More information about the gromacs.org_gmx-users mailing list