[gmx-users] pdb2gmx disulfide bond formation - missing bond, angle, & dihedral types with all GROMOS FFs
Elizabeth Ploetz
ploetz at ksu.edu
Wed Nov 23 00:32:28 CET 2011
Greetings Gromacs Users,
I am building the topology file for a protein with three disulfide bonds (bovine pancreatic trpysin inhibitor). When using any of the GROMOS FFs the topol.top output of pdb2gmx has missing bond, angle, and dihedral types on the lines describing the three disulfides. (The residue names do change appropriately i.e., CYS becomes CYS2.) The disulfides do form correctly when using the other currently available FFs. All the output shown below my message is from running GROMACS-4.5.5. Note the same thing happens when running GROMACS-4.5.3 and GROMACS-4.0.5.
I have not found any discussion of this issue on the internet (in general) or the gmx mailing list (specifically), however I suspect this may have contributed to at least one user message ( http://lists.gromacs.org/pipermail/gmx-users/2011-March/059242.html ). It is trivial to fill in the missing bond, angle, and dihedral types by hand after running pdb2gmx (this may be why this has not been discussed too much), but I am interested in figuring out a long term solution because the lab I work in has developed a FF which uses the GROMOS bonds and angles (and thus also uses the same format as GROMOS does for the ffbonded.itp file). We hope to have our FF supported by GROMACS in the future, but we want to make sure that GROMACS users would not encounter this problem if they selected our FF.
Could anyone point me in the right direction?
Thanks for your consideration of this!
All the best,
Elizabeth A. Ploetz
Kansas State University
The list below shows the tested FFs. A '+' indicates proper disulfide description in the topology file, and an 'X' indicates the output contained missing bond/angle/dihedral types.
Test of disulfide bond formation using pdb2gmx and FFs available in GROMACS-4.5.5:
+ 1: AMBER03 protein, nucleic AMBER94 (Duan et al., J. Comp. Chem. 24, 1999-2012, 2003)
+ 2: AMBER94 force field (Cornell et al., JACS 117, 5179-5197, 1995)
+ 3: AMBER96 protein, nucleic AMBER94 (Kollman et al., Acc. Chem. Res. 29, 461-469, 1996)
+ 4: AMBER99 protein, nucleic AMBER94 (Wang et al., J. Comp. Chem. 21, 1049-1074, 2000)
+ 5: AMBER99SB protein, nucleic AMBER94 (Hornak et al., Proteins 65, 712-725, 2006)
+ 6: AMBER99SB-ILDN protein, nucleic AMBER94 (Lindorff-Larsen et al., Proteins 78, 1950-58, 2010)
+ 7: AMBERGS force field (Garcia & Sanbonmatsu, PNAS 99, 2782-2787, 2002)
+ 8: CHARMM27 all-atom force field (with CMAP) - version 2.0
X 9: GROMOS96 43a1 force field
X10: GROMOS96 43a2 force field (improved alkane dihedrals)
X11: GROMOS96 45a3 force field (Schuler JCC 2001 22 1205)
X12: GROMOS96 53a5 force field (JCC 2004 vol 25 pag 1656)
X13: GROMOS96 53a6 force field (JCC 2004 vol 25 pag 1656)
+14: OPLS-AA/L all-atom force field (2001 aminoacid dihedrals)
+15: [DEPRECATED] Encad all-atom force field, using full solvent charges
+16: [DEPRECATED] Encad all-atom force field, using scaled-down vacuum charges
+17: [DEPRECATED] Gromacs force field (see manual)
+18: [DEPRECATED] Gromacs force field with hydrogens for NMR
This is an example of how I ran pdb2gmx:
:-) G R O M A C S (-:
Gromacs Runs On Most of All Computer Systems
:-) VERSION 4.5.5 (-:
.
. skipping
.
Select the Force Field:
>From '/usr/local/gromacs/share/gromacs/top':
1: AMBER03 protein, nucleic AMBER94 (Duan et al., J. Comp. Chem. 24, 1999-2012, 2003)
2: AMBER94 force field (Cornell et al., JACS 117, 5179-5197, 1995)
3: AMBER96 protein, nucleic AMBER94 (Kollman et al., Acc. Chem. Res. 29, 461-469, 1996)
4: AMBER99 protein, nucleic AMBER94 (Wang et al., J. Comp. Chem. 21, 1049-1074, 2000)
5: AMBER99SB protein, nucleic AMBER94 (Hornak et al., Proteins 65, 712-725, 2006)
6: AMBER99SB-ILDN protein, nucleic AMBER94 (Lindorff-Larsen et al., Proteins 78, 1950-58, 2010)
7: AMBERGS force field (Garcia & Sanbonmatsu, PNAS 99, 2782-2787, 2002)
8: CHARMM27 all-atom force field (with CMAP) - version 2.0
9: GROMOS96 43a1 force field
10: GROMOS96 43a2 force field (improved alkane dihedrals)
11: GROMOS96 45a3 force field (Schuler JCC 2001 22 1205)
12: GROMOS96 53a5 force field (JCC 2004 vol 25 pag 1656)
13: GROMOS96 53a6 force field (JCC 2004 vol 25 pag 1656)
14: OPLS-AA/L all-atom force field (2001 aminoacid dihedrals)
15: [DEPRECATED] Encad all-atom force field, using full solvent charges
16: [DEPRECATED] Encad all-atom force field, using scaled-down vacuum charges
17: [DEPRECATED] Gromacs force field (see manual)
18: [DEPRECATED] Gromacs force field with hydrogens for NMR
13
Using the Gromos53a6 force field in directory gromos53a6.ff
Opening force field file /usr/local/gromacs/share/gromacs/top/gromos53a6.ff/watermodels.dat
Select the Water Model:
1: SPC simple point charge, recommended
2: SPC/E extended simple point charge
3: None
1
Opening force field file /usr/local/gromacs/share/gromacs/top/gromos53a6.ff/aminoacids.r2b
Reading ../start.pdb...
Read 'TRYPSIN INHIBITOR', 604 atoms
Analyzing pdb file
Splitting chemical chains based on TER records or chain id changing.
There are 1 chains and 0 blocks of water and 58 residues with 604 atoms
chain #res #atoms
1 ' ' 58 604
All occupancies are one
Opening force field file /usr/local/gromacs/share/gromacs/top/gromos53a6.ff/atomtypes.atp
Atomtype 1
Reading residue database... (gromos53a6)
Opening force field file /usr/local/gromacs/share/gromacs/top/gromos53a6.ff/aminoacids.rtp
Using default: not generating all possible dihedrals
Using default: excluding 3 bonded neighbors
Using default: generating 1,4 H--H interactions
Using default: removing impropers on same bond as a proper
Residue 108
Sorting it all out...
Opening force field file /usr/local/gromacs/share/gromacs/top/gromos53a6.ff/aminoacids.hdb
Opening force field file /usr/local/gromacs/share/gromacs/top/gromos53a6.ff/aminoacids.n.tdb
Opening force field file /usr/local/gromacs/share/gromacs/top/gromos53a6.ff/aminoacids.c.tdb
Processing chain 1 (604 atoms, 58 residues)
Which LYSINE type do you want for residue 15
0. Not protonated (charge 0) (LYS)
1. Protonated (charge +1) (LYSH)
Type a number:1
Which LYSINE type do you want for residue 26
0. Not protonated (charge 0) (LYS)
1. Protonated (charge +1) (LYSH)
.
. skipping
.
Type a number:0
Which GLUTAMIC ACID type do you want for residue 49
0. Not protonated (charge -1) (GLU)
1. Protonated (charge 0) (GLUH)
Type a number:0
Identified residue ARG1 as a starting terminus.
Identified residue ALA58 as a ending terminus.
8 out of 8 lines of specbond.dat converted successfully
Special Atom Distance matrix:
CYS5 CYS14 CYS30 CYS38 CYS51 MET52
SG57 SG136 SG317 SG398 SG543 SD551
CYS14 SG136 2.408
CYS30 SG317 0.828 2.331
CYS38 SG398 2.224 0.204 2.189
CYS51 SG543 0.759 2.165 0.204 2.017
MET52 SD551 0.928 2.703 0.373 2.560 0.550
CYS55 SG585 0.204 2.316 0.664 2.137 0.573 0.805
Link CYS-5 SG-57 and CYS-55 SG-585 (y/n) ?y
Link CYS-14 SG-136 and CYS-38 SG-398 (y/n) ?y
Link CYS-30 SG-317 and CYS-51 SG-543 (y/n) ?y
Select start terminus type for ARG-1
0: NH3+
1: NH2
2: None
0
Start terminus ARG-1: NH3+
Select end terminus type for ALA-58
0: COO-
1: COOH
2: None
0
End terminus ALA-58: COO-
Checking for duplicate atoms....
Now there are 58 residues with 604 atoms
Making bonds...
Number of bonds was 623, now 618
Generating angles, dihedrals and pairs...
Before cleaning: 975 pairs
Before cleaning: 1187 dihedrals
Making cmap torsions...There are 329 dihedrals, 307 impropers, 906 angles
975 pairs, 618 bonds and 0 virtual sites
Total mass 6517.563 a.m.u.
Total charge 6.000 e
Writing topology
Writing coordinate file...
--------- PLEASE NOTE ------------
You have successfully generated a topology from: ../start.pdb.
The Gromos53a6 force field and the spc water model are used.
--------- ETON ESAELP ------------
gcq#81: "Love is Like Moby Dick, Get Chewed and Get Spat Out" (Urban Dance Squad)
Here are the relevant sections of the output topology file when using GROMOS-53a6.
[ atoms ]
.
. skipping
.
; residue 5 CYS rtp CYS2 q 0.0
53 N 5 CYS N 21 -0.31 14.0067 ; qtot 0.69
54 H 5 CYS H 21 0.31 1.008 ; qtot 1
55 CH1 5 CYS CA 22 0 13.019 ; qtot 1
56 CH2 5 CYS CB 22 0 14.027 ; qtot 1
57 S 5 CYS SG 22 0 32.06 ; qtot 1
58 C 5 CYS C 23 0.45 12.011 ; qtot 1.45
59 O 5 CYS O 23 -0.45 15.9994 ; qtot 1
.
. skipping
.
; residue 14 CYS rtp CYS2 q 0.0
132 N 14 CYS N 60 -0.31 14.0067 ; qtot -0.31
133 H 14 CYS H 60 0.31 1.008 ; qtot 0
134 CH1 14 CYS CA 61 0 13.019 ; qtot 0
135 CH2 14 CYS CB 61 0 14.027 ; qtot 0
136 S 14 CYS SG 61 0 32.06 ; qtot 0
137 C 14 CYS C 62 0.45 12.011 ; qtot 0.45
138 O 14 CYS O 62 -0.45 15.9994 ; qtot 0
.
. skipping
.
; residue 30 CYS rtp CYS2 q 0.0
313 N 30 CYS N 133 -0.31 14.0067 ; qtot 3.69
314 H 30 CYS H 133 0.31 1.008 ; qtot 4
315 CH1 30 CYS CA 134 0 13.019 ; qtot 4
316 CH2 30 CYS CB 134 0 14.027 ; qtot 4
317 S 30 CYS SG 134 0 32.06 ; qtot 4
318 C 30 CYS C 135 0.45 12.011 ; qtot 4.45
319 O 30 CYS O 135 -0.45 15.9994 ; qtot 4
.
. skipping
.
; residue 38 CYS rtp CYS2 q 0.0
394 N 38 CYS N 170 -0.31 14.0067 ; qtot 3.69
395 H 38 CYS H 170 0.31 1.008 ; qtot 4
396 CH1 38 CYS CA 171 0 13.019 ; qtot 4
397 CH2 38 CYS CB 171 0 14.027 ; qtot 4
398 S 38 CYS SG 171 0 32.06 ; qtot 4
399 C 38 CYS C 172 0.45 12.011 ; qtot 4.45
400 O 38 CYS O 172 -0.45 15.9994 ; qtot 4
.
. skipping
.
; residue 51 CYS rtp CYS2 q 0.0
539 N 51 CYS N 225 -0.31 14.0067 ; qtot 5.69
540 H 51 CYS H 225 0.31 1.008 ; qtot 6
541 CH1 51 CYS CA 226 0 13.019 ; qtot 6
542 CH2 51 CYS CB 226 0 14.027 ; qtot 6
543 S 51 CYS SG 226 0 32.06 ; qtot 6
544 C 51 CYS C 227 0.45 12.011 ; qtot 6.45
545 O 51 CYS O 227 -0.45 15.9994 ; qtot 6.
.
. skipping
.
; residue 55 CYS rtp CYS2 q 0.0
581 N 55 CYS N 241 -0.31 14.0067 ; qtot 6.69
582 H 55 CYS H 241 0.31 1.008 ; qtot 7
583 CH1 55 CYS CA 242 0 13.019 ; qtot 7
584 CH2 55 CYS CB 242 0 14.027 ; qtot 7
585 S 55 CYS SG 242 0 32.06 ; qtot 7
586 C 55 CYS C 243 0.45 12.011 ; qtot 7.45
587 O 55 CYS O 243 -0.45 15.9994 ; qtot 7
.
. skipping
.
[ bonds ]
.
. skipping
.
56 57 2 gb_32
57 585 2
58 59 2 gb_5
.
. skipping
.
135 136 2 gb_32
136 398 2
137 138 2 gb_5
.
. skipping
.
316 317 2 gb_32
317 543 2
318 319 2 gb_5
.
. skipping
.
[ angles ]
.
. skipping
.
55 56 57 2 ga_16
56 57 585 2
55 58 59 2 ga_30
.
. skipping
.
134 135 136 2 ga_16
135 136 398 2
134 137 138 2 ga_30
.
. skipping
.
315 316 317 2 ga_16
316 317 543 2
315 318 319 2 ga_30
.
. skipping
.
396 397 398 2 ga_16
136 398 397 2
396 399 400 2 ga_30
.
. skipping
.
541 542 543 2 ga_16
317 543 542 2
541 544 545 2 ga_30
.
. skipping
.
583 584 585 2 ga_16
57 585 584 2
583 586 587 2 ga_30
.
. skipping
.
[ dihedrals ]
.
. skipping
.
53 55 58 60 1 gd_40
55 56 57 585 1
56 57 585 584 1
55 58 60 62 1 gd_14
.
. skipping
.
132 134 137 139 1 gd_40
134 135 136 398 1
135 136 398 397 1
134 137 139 141 1 gd_14
.
. skipping
.
313 315 318 320 1 gd_40
315 316 317 543 1
316 317 543 542 1
315 318 320 322 1 gd_14
.
. skipping
.
394 396 399 401 1 gd_40
396 397 398 136 1
396 399 401 403 1 gd_14
.
. skipping
.
539 541 544 546 1 gd_40
541 542 543 317 1
541 544 546 548 1 gd_14
.
. skipping
.
581 583 586 588 1 gd_40
583 584 585 57 1
583 586 588 590 1 gd_14
.
. skipping
.
The GROMOS FFs all use a 'specbonds' section at the end of their ffbonded.itp files, which looks like this (below is an excerpt from gromos53a6.ff/ffbonded.itp):
; bond-, angle- and dihedraltypes for specbonds:
[ bondtypes ]
S S 2 gb_36
NR FE 2 gb_34
[ angletypes ]
CH1 CH2 S 2 ga_16
CH2 S S 2 ga_6
CR1 NR FE 2 ga_34
NR FE NR 2 ga_17
[ dihedraltypes ]
S S 1 gd_21
NR FE 1 gd_38
CH2 S 1 gd_26
while the other FFs do not use this method (as shown below).
Elizabeths-MacBook-Pro:top elizabethploetz$ pwd
/usr/local/gromacs/share/gromacs/top
Elizabeths-MacBook-Pro:top elizabethploetz$ grep 'specbond' */*
gromos43a1.ff/ffbonded.itp:; bond-, angle- and dihedraltypes for specbonds:
gromos43a2.ff/ffbonded.itp:; bond-, angle- and dihedraltypes for specbonds:
gromos45a3.ff/ffbonded.itp:; bond-, angle- and dihedraltypes for specbonds:
gromos53a5.ff/ffbonded.itp:; bond-, angle- and dihedraltypes for specbonds:
gromos53a6.ff/ffbonded.itp:; bond-, angle- and dihedraltypes for specbonds:
In a quick and dirty effort to mimic the other (working) FFs, I copied the /usr/local/gromacs/share/gromacs/top/gromos53a6.ff files into my local directory, commented out the 'specbonds' section of the ffbonded.itp file, and re-ran pdb2gmx using the local files. This did not change the results however.
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