How do you deal with proteins having large loop?

User discussions
1

GROMACS version: GROMACS 2023.3
GROMACS modification: No

I am preparing files for protein-ligand simulation for PPAR alpha. The protein structure available on PDB has two truncated loops. These truncated loops introduced the artifact of long bond distances during energy minimization. If I include the loop, the system will be very large, and the simulation will unnecessarily involve extra costs. The loops have no role in the binding of the ligand.

PDB Entry: PDB 7bq3 structure summary ‹ Protein Data Bank in Europe (PDBe) ‹ EMBL-EBI
AlphaFold Entry: AlphaFold Protein Structure Database

Possible solution: Use a coarse-graining tool like MARTINI, SIRAH, or VOTCA to create a coarse-grained representation of the truncated loop. Never done before. Not sure if it’s possible, but I’m going to try.

Have you any idea how to deal with this situation?

@jalemkul Would appreciate your take on this.

2

Hi,

In cases such as you described, it’s quite customary to omit flexible regions that do not affect the relevant outcomes of our simulation. If you introduce a terminus that isn’t a natural C- or N-term, though, remember to use the NME/ACE capping residues to avoid artificially introducing extra charges to the system. In the PDB file, mark the two parts as separate chains, or add a TER entry in between them, to avoid the “long bond” issue in pdb2gmx.

Best,
MW