[gmx-users] Unstable Minimizations
Jack Shultz
js at drugdiscoveryathome.com
Thu Jan 14 17:41:28 CET 2010
Problem Solved.
I replaced HETATM with ATOM, I fixed BOTH N-terminal and C-terminal. I kept
TER and END. Removed all CONECT. Renamed the CYS to CYS2. No other
non-AminoAcid residues were present. Most of this is described by the
FFAmber site
http://chemistry.csulb.edu/ffamber/
2)
*(!) Residue Nomenclature:* Residues in the AMBER ports are named according
to their position in the sequence (i.e. terminal, non-terminal, monomer)
following standard AMBER conventions. For this reason, it may be necessary
to rename residues in the .pdb file you will import beforehand. Please note
that all residues are named in the residue topology files (i.e.
ffamber*.rtp), so if you are unsure of the correct residue name to use, you
should be able to find it there. The .rtp files are ordered as follows:
water models (TIP), ions & urea (URE), peptide terminal capping residues
(ie. ACE, NH2, NMe), non-terminal amino acids (i.e. TYR, ALA), non-terminal
acidic amino acids (i.e. ASH, GLH, etc.), C-terminal amino acids (i.e. CALA,
CGLY), N-terminal amino acids (i.e. NALA, NGLY), and all nucleic acid
residues. Nucleic acids listed at the end of each .rtp follow the following
order for each residue type: DNA is first, followed by RNA, in the order
5'-term, 3'-term, non-terminal, and monomer. The three .pdb files above are
examples of how pdb files shoud be modified. Residues in the ffamber ports
have been named as follows: *(a)*
*Non-terminal amino and nucleic acid residues* follow standard AMBER naming
conventions. To avoid confusion between GROMACS and AMBER conventions, we
have omitted the redundant HIS residue, leaving HID, HIE, HIP, and terminal
versions of these topologies. Additionally, due to the automated changing of
certain residue names by pdb2gmx, the LYS and CYS residues have been renamed
LYP (Lysine plus) and CYN (Cysteine neutral, compared to AMBER residue CYM =
Cysteine minus).
*(b)*
*C- and N-terminal amino acids* include a C or N prefix respectively, so
C-terminal ALA is CALA and N-ternimal PHE is NPHE. As with non-terminal
versions, the LYS and CYS terminal residues are listed as NLYP,CLYP and
NCYN,CCYN.
*(c)*
*Nucleic acid residues* come in four flavors. All residue names include XY,
where X = D or R for DNA or RNA respectively, and Y = first letter of the
nucleotide name. A suffix (XY*Z*) is added for monomers (Z=N), 5'-terminal
(Z=5), and 3'-terminal (Z=3) residues. For example, 3'-term DNA Cytosine =
"DC3", 5'-term RNA Cytosine = "RC5", non-terminal DNA Cytosine = "DC", and
lone RNA Cytosine monomer = "RCN".
*(d)*
*Cys disulfide bonds* can be instituted by changing the names of the CYS
residues involved in the disulfide bonds to CYS2.
On Mon, Jan 11, 2010 at 11:57 AM, Justin A. Lemkul <jalemkul at vt.edu> wrote:
>
>
> 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
>>
>> ========================================
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>>
>>
>> --
>> 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>
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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
>
> ========================================
> --
> gmx-users mailing list 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
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>
--
Jack
http://drugdiscoveryathome.com
http://hydrogenathome.org
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