To elucidate their reaction mechanisms of metalloproteins at the atomic level, it is necessary to theoretically clarify the three-dimensional structures, especially the roles of each amino acid residue, water molecules, and cofactors that constitute the active center. Our research group has been analyzing the functions of various metalloproteins. Here, I will focus on the following three themes:
(1) Geometry and electronic structures of the active center of HiPIPs.
High-potential iron-sulfur proteins (HiPIPs) has a [4Fe-4S] iron-sulfur cluster (FeS cluster) in its active center, which has an extremely high redox potential compared to ferredoxin, which has a similar cluster. To understand the effects of surrounding environment to the geometrical and electronic structures of FeS clusters in HiPIP, the size dependence of the cluster model of the FeS cluster was investigated by quantum chemical calculations to find why the FeS cluster has a compact structure found in Xray analysis[1].
(2) Species specific regulation of inhibition mechanism of HPPD inhibitor.
A mesotrione is one of the HPPD inhibitor herbicides binds strongly to the broadleaf Arabidopsis HPPD, while they do not bind as strongly to the Embac HPPD. We investigated the structural changes between Arabidopsis and EmbacHPPDs based on free energy analysis using classical MD simulation to clarify the differences in inhibitory activity. Our analyses suggest that the movement of a-Helix differs among plant species in both apo- and holo-forms which regulate the binding and releasing the ligand [2].
(3) Stability and formation of 3D-domain swapping proteins.
The antibody light chain may engage in 3D domain swapping within the variable region (#4VL), potentially forming the tetramer, as revealed in solution and crystal structures. However, the 3D-domain swapping dimers could not be detected experimentally. We have performed the relatively long-time MD simulations to understand why the dimer is missing, by evaluating the solvation free energy difference between tetramer and two diems and stability of dimer itself.
References: (1) A. Sato, Y. Hori, Y. Shigeta, Inorg. Chem. 2023, 62, 2040–2048. (2) Y. Munei et al., J. Agricult. Food Chem. 2023, 71, 9528-9537. (3) L. Duan et al., J. Phys. Chem. B 2024, 128, 9086−9093.