Fragment molecular orbital calculations containing Mg²⁺ ions: PPlase domain of Cyclophilin G

Abstract

We investigated fragmentation methods around metals when performing fragment molecular orbital (FMO) calculations for metal-containing proteins, as well as appropriate structural preprocessing. The protein structure data was employed from the peptidyl prolyl cis/trans isomerase (PPlase) domain of human Cyclophilin G, which contains Mg²⁺ ions (PDBID: 2WFI). The results of the present study revealed three issues: First, it was better to contain Mg²⁺ ions in the same fragment as that for water molecules in the first hydration shell, which was revealed thorough PIEDA (pair interaction energy decomposition analysis) and atomic charge analysis obtained by FMO calculations. Second, while there were two conformers of Phe72 in the PPlase domain of Cyclophilin, we could determine the more appropriate conformer for computational analysis by comparing each energy component of PIEDA. Finally, we derived the optimal constraint conditions for the structural optimization of this molecular system in which the exchange repulsion (EX) component of PIEDA took relevant values without deforming the initial structure too much. These findings could be applied to FMO calculations for other proteins as well.