Dear All,
I have tried to build topology file for a structure that has covalent bond (Between ligand and protein) by using pdb2gmx with the following command:
pdb2gmx -f WILD0MODEL.B99990001.pdb -o conf.pdb
Where I have tried with three following force fields and water model
1.Amber99sb
2.OPLS-AA/L all-atom force field (2001 aminoacid dihedrals)
3.CHARMM27 all-atom force field (with CMAP) - version 2.0
1.TIP4P TIP 4-point, recommended
But i get the following error:
ERROR:
Writing topology
Processing chain 2 'A' (11 atoms, 1 residues)
Warning: Starting residue BGC505 in chain not identified as Protein/RNA/DNA.
Problem with chain definition, or missing terminal residues.
This chain does not appear to contain a recognized chain molecule.
If this is incorrect, you can edit residuetypes.dat to modify the behavior.
8 out of 8 lines of specbond.dat converted successfully
-------------------------------------------------------
Program pdb2gmx, VERSION 4.6.1
Source code file: /Users/Mahesh/Applications/gromacs-4.6.1/src/kernel/resall.c, line: 642
Fatal error:
Residue 'BGC' not found in residue topology database
From the error, I have understood that the reason for error is presence of non standard residue in structure coordinate file.
So, I have generated topology file for BGC(D-Glucose) through prodrug and replace the existing HETATM coordinates by the same but the final minimized structure doesn't even have ligand. (I am not sure this is correct way)
So, If someone knows how to create topology file for structure that has covalent link between residue and ligand.
Thanking you in advance
http://www.gromacs.org/Documentation/How-tos/Adding_a_Residue_to_a_Force_Field
You need to create an .rtp entry for a custom residue that contains the amino acid linked to the covalent adduct. Do not use PRODRG parameters; they are of insufficient quality for MD simulations without significant refinement. Moreover, PRODRG is to be used only with GROMOS parameter sets, not any of those you have listed above.
Dear Justin,
Many more thanks but could you give me any example for step by step .rtp file creation.
Thanking you in advance
The file format is described in the GROMACS manual, Chapter 5. All you're doing is modifying an existing amino acid to create a new residue, so copy the contents of that amino acid into a newly named residue definition and modify as needed.
Dear Justin,
This is my modeled structure
LINK C1 BGC A 505 OD2 ASP A 192 1555 1555 1.49
ATOM 1 N MET A 1 24.302 64.094 -59.895 1.00 25.08 N
ATOM 2 CA MET A 1 25.597 64.337 -59.199 1.00 22.91 C
ATOM 3 C MET A 1 26.726 64.293 -60.221 1.00 22.81 C
ATOM 4 O MET A 1 26.804 63.351 -61.014 1.00 23.00 O
ATOM 5 CB MET A 1 25.810 63.286 -58.091 1.00 22.78 C
ATOM 6 CG MET A 1 26.934 63.614 -57.110 1.00 21.69 C
ATOM 7 SD MET A 1 27.096 62.493 -55.701 1.00 21.64 S
ATOM 8 CE MET A 1 25.612 62.862 -54.789 1.00 20.43 C
.
.
ATOM 1536 N ASP A 192 21.763 61.500 -42.930 1.00 23.26 N
ATOM 1537 CA ASP A 192 22.450 60.760 -41.874 1.00 23.10 C
ATOM 1538 C ASP A 192 21.481 59.958 -41.016 1.00 23.23 C
ATOM 1539 O ASP A 192 20.419 60.457 -40.621 1.00 22.22 O
ATOM 1540 CB ASP A 192 23.284 61.722 -41.002 1.00 25.40 C
ATOM 1541 CG ASP A 192 23.930 61.035 -39.785 1.00 27.69 C
ATOM 1542 OD1 ASP A 192 23.418 61.230 -38.655 1.00 29.53 O
ATOM 1543 OD2 ASP A 192 25.098 60.228 -39.969 1.00 28.06 O1-
.
.
ATOM 3960 N ALA A 504 46.284 63.907 -71.577 1.00 35.11 N
ATOM 3961 CA ALA A 504 46.855 64.837 -72.555 1.00 37.20 C
ATOM 3962 C ALA A 504 46.040 66.119 -72.719 1.00 38.54 C
ATOM 3963 O ALA A 504 44.802 66.020 -72.846 1.00 40.48 O
ATOM 3964 CB ALA A 504 47.008 64.143 -73.892 1.00 35.72 C
ATOM 3965 OXT ALA A 504 46.654 67.208 -72.691 1.00 41.98 O1-
TER 3966 ALA A 504
HETATM 3967 C2 BGC A 505 27.366 59.540 -39.061 1.00 28.08 C
HETATM 3968 C3 BGC A 505 28.063 59.219 -37.697 1.00 28.15 C
HETATM 3969 C4 BGC A 505 27.184 59.603 -36.510 1.00 27.68 C
HETATM 3970 C5 BGC A 505 25.841 58.850 -36.553 1.00 27.24 C
HETATM 3971 C6 BGC A 505 24.729 59.619 -35.854 1.00 29.21 C
HETATM 3972 C1 BGC A 505 25.810 59.270 -39.070 1.00 30.28 C
HETATM 3973 O2 BGC A 505 28.005 58.761 -40.050 1.00 29.46 O
HETATM 3974 O3 BGC A 505 29.303 59.931 -37.597 1.00 24.50 O
HETATM 3975 O4 BGC A 505 27.858 59.293 -35.303 1.00 23.23 O
HETATM 3976 O5 BGC A 505 25.364 58.473 -37.919 1.00 30.31 O
HETATM 3977 O6 BGC A 505 24.636 60.976 -36.259 1.00 29.14 O
CONECT 1543 3972
CONECT 3967 3968 3972 3973
CONECT 3968 3967 3969 3974
CONECT 3969 3968 3970 3975
CONECT 3970 3969 3971 3976
CONECT 3971 3970 3977
CONECT 3972 1543 3967 3976
CONECT 3973 3967
CONECT 3974 3968
CONECT 3975 3969
CONECT 3976 3970 3972
CONECT 3977 3971
END
1. As you said i have included ligand (B-D-glucose) in aminoacid.rtp file
[ BGC ]
[ atoms ]
C4 CH1R 0.23200 1
O4 OA -0.64200 1
HO4 H 0.41000 1
C3 CH1R 0.23200 2
O3 OA -0.64200 2
HO3 H 0.41000 2
C2 CH1R 0.23200 3
O2 OA -0.64200 3
HO2 H 0.41000 3
C6 CH2 0.23200 4
O6 OA -0.64200 4
HO6 H 0.41000 4
C5 CH1R 0.23200 5
O5 OR -0.46400 5
C1 CH1R 0.46400 5
O1 OA -0.64200 5
HO1 H 0.41000 5
[ bonds ]
HO4 O4 gb_1
O2 HO2 gb_1
O3 HO3 gb_1
O6 HO6 gb_1
O1 HO1 gb_1
O4 C4 gb_20
C4 C3 gb_26
C4 C5 gb_26
C2 O2 gb_20
C2 C3 gb_26
C2 C1 gb_26
C3 O3 gb_20
C6 O6 gb_20
C6 C5 gb_26
C5 O5 gb_20
O5 C1 gb_20
C1 O1 gb_20
[ angles ]
; ai aj ak gromos type
HO4 O4 C4 ga_12
C2 O2 HO2 ga_12
C3 O3 HO3 ga_12
C6 O6 HO6 ga_12
C1 O1 HO1 ga_12
O4 C4 C3 ga_9
O4 C4 C5 ga_9
C3 C4 C5 ga_8
O2 C2 C3 ga_9
O2 C2 C1 ga_9
C3 C2 C1 ga_8
C4 C3 C2 ga_8
C4 C3 O3 ga_9
C2 C3 O3 ga_9
O6 C6 C5 ga_9
C4 C5 C6 ga_8
C4 C5 O5 ga_9
C6 C5 O5 ga_9
C5 O5 C1 ga_10
C2 C1 O5 ga_9
C2 C1 O1 ga_9
O5 C1 O1 ga_9
[ impropers ]
; ai aj ak al gromos type
C2 C3 C1 O2 gi_2
C3 C2 C4 O3 gi_2
O4 C3 C5 C4 gi_2
C5 C4 O5 C6 gi_2
O1 C2 O5 C1 gi_2
[ dihedrals ]
; ai aj ak al gromos type
HO2 O2 C2 C1 gdc_t3 ; [T3: X-C-O-H (generic hydroxyl)]
C2 C3 O3 HO3 gdc_t3 ; [T3: X-C-O-H (generic hydroxyl)]
C3 C4 O4 HO4 gdc_t3 ; [T3: X-C-O-H (generic hydroxyl)]
C5 C6 O6 HO6 gdc_t3 ; [T3: X-C-O-H (generic hydroxyl)]
O5 C1 O1 HO1 gdc_t3 ; [T3: X-C-O-H (generic hydroxyl)]
O5 C1 O1 HO1 gdc_t4 ; [T4: Or-CH*r-O-X (exo-anomeric)]
O2 C2 C3 O3 gdc_t12; [T12: Ox-X-X-Ox; not type T13(oxygen-oxygen gauche)]
C1 C2 C3 C4 gdc_t1 ; [T1: X-C-C-X; X not H (generic CC -unaltered from 53A6)]
O2 C2 C1 O5 gdc_t13; [T13: Ox-X-X-Or (oxygen-oxygenintracyclic)]
O2 C2 C1 O1 gdc_t12; [T12: Ox-X-X-Ox; not type T13(oxygen-oxygen gauche)]
C3 C2 C1 O5 gdc_t1 ; [T1: X-C-C-X; X not H (generic CC -unaltered from 53A6)]
C2 C3 C4 C5 gdc_t1 ; [T1: X-C-C-X; X not H (generic CC -unaltered from 53A6)]
O3 C3 C4 O4 gdc_t12; [T12: Ox-X-X-Ox; not type T13 (oxygen-oxygen gauche)]
C3 C4 C5 O5 gdc_t1 ; [T1: X-C-C-X; X not H (generic CC -unaltered from 53A6)]
O4 C4 C5 O5 gdc_t13; [T13: Ox-X-X-Or (oxygen-oxygenintracyclic)]
O6 C6 C5 C4 gdc_t1 ; [T1: X-C-C-X; X not H (generic CC -unaltered from 53A6)]
O6 C6 C5 C4 gdc_t10; [T10: Xr-CH*r-CH*-O (exocyclicoxymethyl)]
O6 C6 C5 O5 gdc_t11; [T11: Xr-CH*r-CH*-O (exocyclicoxymethyl)]
O6 C6 C5 O5 gdc_t12; [T12: Ox-X-X-Ox; not type T13(oxygen-oxygen gauche)]
C4 C5 O5 C1 gdc_t2 ; [T2: X-C-O-X; X not H (generic CO)]
C5 O5 C1 C2 gdc_t2 ; [T2: X-C-O-X; X not H (generic CO)]
C5 O5 C1 O1 gdc_t5 ; [T5: CH*r-Or-CH*r-O (anomeric)]
[ exclusions ]
C6 O1
C6 O3
HO1 C5
HO1 C3
HO2 C4
HO2 O5
HO3 C1
HO3 C5
HO4 C2
HO4 O5
2. I have added covalent link details in specbond.dat
11
ASP OD2 1 BGC C1 1 1.49 ASP BGC
BGC C1 1 ASP OD2 1 1.49 BGC ASP
BGC C2 1 BGC O5 1 1.49 BGC BGC
CYS SG 1 CYS SG 1 0.2 CYS2 CYS2
CYS SG 1 HEM FE 2 0.25 CYS2 HEME
CYS SG 1 HEM CAB 1 0.18 CYS2 HEME
CYS SG 1 HEM CAC 1 0.18 CYS2 HEME
HIS NE2 1 HEM FE 1 0.2 HIS1 HEME
MET SD 1 HEM FE 1 0.24 MET HEME
CO C 1 HEME FE 1 0.19 CO HEME
CYM SG 1 CYM SG 1 0.2 CYS2 CYS2
3. I have added h atom in aminoacids.hdb
BGC 4
1 2 HO2 O2 C2 C3
1 2 HO3 O3 C3 C2
1 2 HO4 O4 C4 C5
1 2 HO6 O6 C6 C5
after all this modification i can able to run successfully but there is no ligand either covalent in minimized structure.
May I know what are all the possible reasons for the same?
Thanking you in advance
Your example is a non-covalent ligand, so the story keeps changing here. The approach outlined in your last reply is for a non-covalent ligand, which is a different approach entirely. As for the last question, things can't magically disappear. Either the species is present in the coordinates and topology or it is not.
Dear Justin,
Thanks and i will consider your suggestion to do find a correct approach to do it.
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