GROMACS version: 2024.2
GROMACS modification: No
Forcefield: CHARMM36m
I’m working with a unique cyclic peptide structure and encountering challenges using GROMACS’ pdb2gmx. The peptide has the following characteristics:
- 16 amino acid residues in total
- Cyclized via an acetyl (ACE) group connecting the 1st and 15th residues
- The N-terminus of the 1st residue is bonded to the ACE carbonyl
- The 15th residue is attached to the ACE methyl group (CH2 now) which is bonded to SG atom of Cys.
- The 16th residue has a free C-terminus (COO-)
When I run pdb2gmx with the command:
gmx pdb2gmx -f prot_pep.pdb -o prot_pep.gro -ter -ignh
pdb2gmx correctly identifies the protein termini (NH3+ and COO-) but fails to recognize the peptide’s cyclic nature. It adds hydrogens inappropriately, particularly at the bond crucial for maintaining the cyclic structure, effectively breaking the cycle.
At the first attempt I accepted the breaking of the peptide to make sure all other stuff (naming, hydrogen, protonation state for the remaining residues in both the protein and the peptide) pass the defaults of pdb2gmx. After that I modified the PDB to remove the extra hydrogens (see image below) that cause the bond to break and tried the pdb2gmx again with -noignh, but no success. I thought the presence of CONECT record in the PDB files might help but Gromacs ignores it.
My question is: How can I properly process this cyclic peptide while maintaining its cyclic structure?
Any guidance would be greatly appreciated.
