Development of CHARMM36-compatible parameters for siroheme group and molecular dynamics simulations of dissimilatory...

Density functional theory (DFT) calculations were used to obtain parameters compatible with the CHARMM36 force field for the siroheme (SRM) group, an iron-containing porphyrin prosthetic cofactor (iron-tetrahydroporphyrin), present in the active site of the dissimilatory sulfite reductase enzyme (DSrAB). The DFT parameters were incorporated into the CHARMM36 force field and validated by 200 ns of classical atomistic molecular dynamics (MD) simulations with the GROMACS software. All parameters, including bond lengths, bond angles, proper and improper dihedral angles, remained stable throughout the entire simulation of three DSrAB systems (PDB codes: 3MM5, 3MM6, and 3MM8). The root mean square deviation (RMSD) profile and hydrogen bond (H-bond) pattern for both SRM groups in each DSrAB system showed that these groups remained stable in their binding sites. The measured distances of relevant interactions involving these groups were consistent with their persistence within their respective binding regions. The developed parameters reproduced the DSrAB enzyme behavior, therefore they can be used in works involving MD simulations of systems containing the siroheme groups.