FMO calculations for zinc metalloprotease:Fragmentation of amino-acid residues coordinated to zinc ion

FMOe: Preprocessing and visualizing package of the fragment molecular orbital method for Molecular Operating Environment and its applications in covalent ligand and metalloprotein analyses

“…The cyclic peptide has the sequence KLqeXHklQEXhKLqeXHklQEXh, where X represents α-aminoisobutyric acid (AIB), and upper-and lower-case letters indicate L-and D-amino acids, respectively. Treating a Zn 2+ ion as a single fragment worsens the self-consistent field convergence of monomers of the ion, the amino acid residue fragments coordinated with it, and dimers containing the ion 28 . This is because the proper electronic state cannot be solved, as the coordination bond is broken.…”

“…Thus, treating the Zn 2+ ion and the histidines in the vicinity coordinated with the ion as one fragment is necessary to avoid breaking the coordination bond. However, a large fragment will be formed if this merging process is performed on a fragment of a typical amino acid residue unit 28 ; this fragmentation scheme is referred to here as "main chain fragmentation" (Figure 4b). The total computational cost of whole protein increases even if one large fragment is included.…”

“…The total computational cost of whole protein increases even if one large fragment is included. Therefore, it is practical to reduce the cost of calculation by dividing the histidine fragment coordinated with the Zn 2+ ions into the main and side chains and merging only the side chain with the Zn 2+ ions (Figures 4c and 4d); the main/side chain (CB-CA) fragmentation, as seen in Figure 4c, is a method that has often been performed in the past [28][29][30] , while the main/side chain (CB-CG) fragmentation, as seen in Figure 4d, is the first attempt to validate the accuracy of metalloprotein fragmentation. However, because this fragmentation process is very complicated to handle manually, we implemented the merge function to be efficiently executed by FMOe.…”