This script makes a cyclic peptide or cyclic nucleotide topology file for GROMACS molecular dynamics program out of the (specially prepared) linear molecule topology file.
This script was developed at the Department of Bionformatics which is a part of the Institute of Biotechnology, Life Sciences Center, Vilnius University. The script was written by V. Kairys visvaldas.kairys(at)bti.vu.lt. You can find other useful bioinfomatics software on our web site http://www.bti.vu.lt/en/departments/department-of-bioinformatics/software.
(1) First step, take your cyclic peptide/nucleotide pdb file and imagine it’s linear (for a moment).
Add using text editor additional 2 additional residues to N and C termini.
The additional residues should be as follows. The one added in the beginning should be taken from the end, and the one added to the end should be taken from the beginning.
for example, your cyclic peptide is MKSY
you have to make a pdb file of peptide YMKSYM
I highlighted the additional residues. The idea is : M has to follow after Y in the beginning (in the final cyclic petide; imagine the sequence going in circles), and M has to follow after Y in the end.
How you make the PDB file: Just COPY the Y into the beginning, and M into the the end.
Example:
You original PDB file:
ATOM 1 N MET A 1 82.620 48.430 -43.970 1.00 0.00 N
ATOM 2 CA MET A 1 81.410 47.750 -44.520 1.00 0.00 C
ATOM 3 CB MET A 1 81.670 46.260 -44.760 1.00 0.00 C
ATOM 4 CG MET A 1 80.870 45.660 -45.990 1.00 0.00 C
ATOM 5 SD MET A 1 79.050 45.500 -45.570 1.00 0.00 S
ATOM 6 CE MET A 1 78.680 45.540 -47.360 1.00 0.00 C
ATOM 7 C MET A 1 80.260 48.000 -43.630 1.00 0.00 C
ATOM 8 O MET A 1 79.720 49.090 -43.630 1.00 0.00 O
ATOM 9 N LYS A 2 79.800 47.030 -42.770 1.00 0.00 N
ATOM 10 CA LYS A 2 78.600 47.090 -41.990 1.00 0.00 C
ATOM 11 CB LYS A 2 78.420 45.710 -41.280 1.00 0.00 C
ATOM 12 CG LYS A 2 79.630 45.060 -40.670 1.00 0.00 C
ATOM 13 CD LYS A 2 79.390 43.670 -40.080 1.00 0.00 C
ATOM 14 CE LYS A 2 80.680 42.900 -39.920 1.00 0.00 C
ATOM 15 NZ LYS A 2 81.570 43.630 -38.990 1.00 0.00 N
ATOM 16 C LYS A 2 78.580 48.190 -40.960 1.00 0.00 C
ATOM 17 O LYS A 2 79.660 48.520 -40.400 1.00 0.00 O
ATOM 18 N SER A 3 77.400 48.800 -40.790 1.00 0.00 N
ATOM 19 CA SER A 3 77.280 50.040 -40.030 1.00 0.00 C
ATOM 20 CB SER A 3 76.560 51.140 -40.790 1.00 0.00 C
ATOM 21 OG SER A 3 77.380 51.610 -41.840 1.00 0.00 O
ATOM 22 C SER A 3 76.610 49.650 -38.690 1.00 0.00 C
ATOM 23 O SER A 3 75.510 49.110 -38.660 1.00 0.00 O
ATOM 24 N TYR A 4 77.300 49.890 -37.600 1.00 0.00 N
ATOM 25 CA TYR A 4 76.860 49.700 -36.270 1.00 0.00 C
ATOM 26 CB TYR A 4 78.030 49.390 -35.290 1.00 0.00 C
ATOM 27 CG TYR A 4 78.720 48.100 -35.660 1.00 0.00 C
ATOM 28 CD1 TYR A 4 79.780 48.090 -36.570 1.00 0.00 C
ATOM 29 CE1 TYR A 4 80.340 46.910 -36.930 1.00 0.00 C
ATOM 30 CZ TYR A 4 79.960 45.710 -36.360 1.00 0.00 C
ATOM 31 OH TYR A 4 80.500 44.450 -36.590 1.00 0.00 O
ATOM 32 CD2 TYR A 4 78.220 46.890 -35.110 1.00 0.00 C
ATOM 33 CE2 TYR A 4 78.840 45.700 -35.460 1.00 0.00 C
ATOM 34 C TYR A 4 76.150 50.920 -35.700 1.00 0.00 C
ATOM 35 O TYR A 4 76.640 52.050 -35.770 1.00 0.00 O
New File, after copying the residues.
ATOM 24 N TYR A 4 77.300 49.890 -37.600 1.00 0.00 N
ATOM 25 CA TYR A 4 76.860 49.700 -36.270 1.00 0.00 C
ATOM 26 CB TYR A 4 78.030 49.390 -35.290 1.00 0.00 C
ATOM 27 CG TYR A 4 78.720 48.100 -35.660 1.00 0.00 C
ATOM 28 CD1 TYR A 4 79.780 48.090 -36.570 1.00 0.00 C
ATOM 29 CE1 TYR A 4 80.340 46.910 -36.930 1.00 0.00 C
ATOM 30 CZ TYR A 4 79.960 45.710 -36.360 1.00 0.00 C
ATOM 31 OH TYR A 4 80.500 44.450 -36.590 1.00 0.00 O
ATOM 32 CD2 TYR A 4 78.220 46.890 -35.110 1.00 0.00 C
ATOM 33 CE2 TYR A 4 78.840 45.700 -35.460 1.00 0.00 C
ATOM 34 C TYR A 4 76.150 50.920 -35.700 1.00 0.00 C
ATOM 35 O TYR A 4 76.640 52.050 -35.770 1.00 0.00 O
ATOM 1 N MET A 1 82.620 48.430 -43.970 1.00 0.00 N
ATOM 2 CA MET A 1 81.410 47.750 -44.520 1.00 0.00 C
ATOM 3 CB MET A 1 81.670 46.260 -44.760 1.00 0.00 C
ATOM 4 CG MET A 1 80.870 45.660 -45.990 1.00 0.00 C
ATOM 5 SD MET A 1 79.050 45.500 -45.570 1.00 0.00 S
ATOM 6 CE MET A 1 78.680 45.540 -47.360 1.00 0.00 C
ATOM 7 C MET A 1 80.260 48.000 -43.630 1.00 0.00 C
ATOM 8 O MET A 1 79.720 49.090 -43.630 1.00 0.00 O
ATOM 9 N LYS A 2 79.800 47.030 -42.770 1.00 0.00 N
ATOM 10 CA LYS A 2 78.600 47.090 -41.990 1.00 0.00 C
ATOM 11 CB LYS A 2 78.420 45.710 -41.280 1.00 0.00 C
ATOM 12 CG LYS A 2 79.630 45.060 -40.670 1.00 0.00 C
ATOM 13 CD LYS A 2 79.390 43.670 -40.080 1.00 0.00 C
ATOM 14 CE LYS A 2 80.680 42.900 -39.920 1.00 0.00 C
ATOM 15 NZ LYS A 2 81.570 43.630 -38.990 1.00 0.00 N
ATOM 16 C LYS A 2 78.580 48.190 -40.960 1.00 0.00 C
ATOM 17 O LYS A 2 79.660 48.520 -40.400 1.00 0.00 O
ATOM 18 N SER A 3 77.400 48.800 -40.790 1.00 0.00 N
ATOM 19 CA SER A 3 77.280 50.040 -40.030 1.00 0.00 C
ATOM 20 CB SER A 3 76.560 51.140 -40.790 1.00 0.00 C
ATOM 21 OG SER A 3 77.380 51.610 -41.840 1.00 0.00 O
ATOM 22 C SER A 3 76.610 49.650 -38.690 1.00 0.00 C
ATOM 23 O SER A 3 75.510 49.110 -38.660 1.00 0.00 O
ATOM 24 N TYR A 4 77.300 49.890 -37.600 1.00 0.00 N
ATOM 25 CA TYR A 4 76.860 49.700 -36.270 1.00 0.00 C
ATOM 26 CB TYR A 4 78.030 49.390 -35.290 1.00 0.00 C
ATOM 27 CG TYR A 4 78.720 48.100 -35.660 1.00 0.00 C
ATOM 28 CD1 TYR A 4 79.780 48.090 -36.570 1.00 0.00 C
ATOM 29 CE1 TYR A 4 80.340 46.910 -36.930 1.00 0.00 C
ATOM 30 CZ TYR A 4 79.960 45.710 -36.360 1.00 0.00 C
ATOM 31 OH TYR A 4 80.500 44.450 -36.590 1.00 0.00 O
ATOM 32 CD2 TYR A 4 78.220 46.890 -35.110 1.00 0.00 C
ATOM 33 CE2 TYR A 4 78.840 45.700 -35.460 1.00 0.00 C
ATOM 34 C TYR A 4 76.150 50.920 -35.700 1.00 0.00 C
ATOM 35 O TYR A 4 76.640 52.050 -35.770 1.00 0.00 O
ATOM 1 N MET A 1 82.620 48.430 -43.970 1.00 0.00 N
ATOM 2 CA MET A 1 81.410 47.750 -44.520 1.00 0.00 C
ATOM 3 CB MET A 1 81.670 46.260 -44.760 1.00 0.00 C
ATOM 4 CG MET A 1 80.870 45.660 -45.990 1.00 0.00 C
ATOM 5 SD MET A 1 79.050 45.500 -45.570 1.00 0.00 S
ATOM 6 CE MET A 1 78.680 45.540 -47.360 1.00 0.00 C
ATOM 7 C MET A 1 80.260 48.000 -43.630 1.00 0.00 C
ATOM 8 O MET A 1 79.720 49.090 -43.630 1.00 0.00 O
I highlighted the copied residues. Notice how atom ordering and residue numbering got messed up.
Next step is renumbering residues (by hand) - important. Renumber first and last residues by hand so that they follow one after another; the TYR will be 0 instead of 4, and the last MET will be 5 instead of 4.
ATOM 24 N TYR A 0 77.300 49.890 -37.600 1.00 0.00 N
ATOM 25 CA TYR A 0 76.860 49.700 -36.270 1.00 0.00 C
ATOM 26 CB TYR A 0 78.030 49.390 -35.290 1.00 0.00 C
ATOM 27 CG TYR A 0 78.720 48.100 -35.660 1.00 0.00 C
ATOM 28 CD1 TYR A 0 79.780 48.090 -36.570 1.00 0.00 C
ATOM 29 CE1 TYR A 0 80.340 46.910 -36.930 1.00 0.00 C
ATOM 30 CZ TYR A 0 79.960 45.710 -36.360 1.00 0.00 C
ATOM 31 OH TYR A 0 80.500 44.450 -36.590 1.00 0.00 O
ATOM 32 CD2 TYR A 0 78.220 46.890 -35.110 1.00 0.00 C
ATOM 33 CE2 TYR A 0 78.840 45.700 -35.460 1.00 0.00 C
ATOM 34 C TYR A 0 76.150 50.920 -35.700 1.00 0.00 C
ATOM 35 O TYR A 0 76.640 52.050 -35.770 1.00 0.00 O
ATOM 1 N MET A 1 82.620 48.430 -43.970 1.00 0.00 N
ATOM 2 CA MET A 1 81.410 47.750 -44.520 1.00 0.00 C
ATOM 3 CB MET A 1 81.670 46.260 -44.760 1.00 0.00 C
ATOM 4 CG MET A 1 80.870 45.660 -45.990 1.00 0.00 C
ATOM 5 SD MET A 1 79.050 45.500 -45.570 1.00 0.00 S
ATOM 6 CE MET A 1 78.680 45.540 -47.360 1.00 0.00 C
ATOM 7 C MET A 1 80.260 48.000 -43.630 1.00 0.00 C
ATOM 8 O MET A 1 79.720 49.090 -43.630 1.00 0.00 O
ATOM 9 N LYS A 2 79.800 47.030 -42.770 1.00 0.00 N
ATOM 10 CA LYS A 2 78.600 47.090 -41.990 1.00 0.00 C
ATOM 11 CB LYS A 2 78.420 45.710 -41.280 1.00 0.00 C
ATOM 12 CG LYS A 2 79.630 45.060 -40.670 1.00 0.00 C
ATOM 13 CD LYS A 2 79.390 43.670 -40.080 1.00 0.00 C
ATOM 14 CE LYS A 2 80.680 42.900 -39.920 1.00 0.00 C
ATOM 15 NZ LYS A 2 81.570 43.630 -38.990 1.00 0.00 N
ATOM 16 C LYS A 2 78.580 48.190 -40.960 1.00 0.00 C
ATOM 17 O LYS A 2 79.660 48.520 -40.400 1.00 0.00 O
ATOM 18 N SER A 3 77.400 48.800 -40.790 1.00 0.00 N
ATOM 19 CA SER A 3 77.280 50.040 -40.030 1.00 0.00 C
ATOM 20 CB SER A 3 76.560 51.140 -40.790 1.00 0.00 C
ATOM 21 OG SER A 3 77.380 51.610 -41.840 1.00 0.00 O
ATOM 22 C SER A 3 76.610 49.650 -38.690 1.00 0.00 C
ATOM 23 O SER A 3 75.510 49.110 -38.660 1.00 0.00 O
ATOM 24 N TYR A 4 77.300 49.890 -37.600 1.00 0.00 N
ATOM 25 CA TYR A 4 76.860 49.700 -36.270 1.00 0.00 C
ATOM 26 CB TYR A 4 78.030 49.390 -35.290 1.00 0.00 C
ATOM 27 CG TYR A 4 78.720 48.100 -35.660 1.00 0.00 C
ATOM 28 CD1 TYR A 4 79.780 48.090 -36.570 1.00 0.00 C
ATOM 29 CE1 TYR A 4 80.340 46.910 -36.930 1.00 0.00 C
ATOM 30 CZ TYR A 4 79.960 45.710 -36.360 1.00 0.00 C
ATOM 31 OH TYR A 4 80.500 44.450 -36.590 1.00 0.00 O
ATOM 32 CD2 TYR A 4 78.220 46.890 -35.110 1.00 0.00 C
ATOM 33 CE2 TYR A 4 78.840 45.700 -35.460 1.00 0.00 C
ATOM 34 C TYR A 4 76.150 50.920 -35.700 1.00 0.00 C
ATOM 35 O TYR A 4 76.640 52.050 -35.770 1.00 0.00 O
ATOM 1 N MET A 5 82.620 48.430 -43.970 1.00 0.00 N
ATOM 2 CA MET A 5 81.410 47.750 -44.520 1.00 0.00 C
ATOM 3 CB MET A 5 81.670 46.260 -44.760 1.00 0.00 C
ATOM 4 CG MET A 5 80.870 45.660 -45.990 1.00 0.00 C
ATOM 5 SD MET A 5 79.050 45.500 -45.570 1.00 0.00 S
ATOM 6 CE MET A 5 78.680 45.540 -47.360 1.00 0.00 C
ATOM 7 C MET A 5 80.260 48.000 -43.630 1.00 0.00 C
ATOM 8 O MET A 5 79.720 49.090 -43.630 1.00 0.00 O
Notice how the residue numbers go from 0 to 5 now.
The atom numbering is in a mess but it’s not important, just the residue numbers are important.
gmx pdb2gmx -f myfile.pdb -o myfile_gmx.pdb
GROMACS creates topology file, write down it’s name (probably topol.top, but could be something else, like .itp file; if .itp is created, you should use it instead of .top for step 3).
gmx_makecyclictop.pl topfile
where topfile is the topology file created in step (2).
The script creates new topology file, e.g. topol_cyc.top.
(4) The hardest part, the topology file, is done. Now we just have to make sure we have the PDB (or GRO) file matching it.
For this, delete the residues added at step (1) from the GROMACS generated file (myfile_gmx.pdb)
Let's say the edited myfile_gmx.pdb without the first and last residues is named myfile_gmx_edit.pdb
Use that file for your simulation purposes, e.g. convert it to GRO and add simulation box:
gmx editconf -f myfile_gmx_edit.pdb -o myfile_gmx_edit.gro -bt cubic -d 1.0
Use myfile_gmx_edit.gro and topol_cyc.top for futher GROMACS simulations.
If you have further questions/bug reports, send email to visvaldas.kairys(at)bti.vu.lt.
Have fun!