title: Multiscale modeling of the active site of [Fe] hydrogenase: the H₂ binding site in open and closed protein conformations.
abstract: A series of QM/MM optimizations of the full protein of [Fe] hydrogenase were performed. The FeGP cofactor has been optimized in the water-bound resting state (1), with a side-on bound dihydrogen (2), or as a hydride intermediate (3). For inclusion of H4MPT in the closed structure, advanced multiscale modeling appears to be necessary, especially to obtain reliable distances between CH-H4MPT(+) and the dihydrogen (H2) or hydride (H(-)) ligand in the FeGP cofactor. Inclusion of the full protein is further important for the relative energies of the two intermediates 2 and 3. We finally find that hydride transfer from 3 has a significantly higher barrier than found in previous studies neglecting the full protein environment.
authors: University of Southern Denmark, Department of Physics, Chemistry and Pharmacy, Campusvej 55, 5230 Odense M (Denmark). edh@sdu.dk.
authors: Erik Donovan
authors: ED
authors: Hedegård
authors: University of Southern Denmark, Department of Physics, Chemistry and Pharmacy, Campusvej 55, 5230 Odense M (Denmark).
authors: Jacob
authors: J
authors: Kongsted
authors: Department of Theoretical Chemistry, Lund University, Getingevägen 60, P.O.Box 124, 221 00 Lund (Sweden).
authors: Ulf
authors: U
authors: Ryde
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D006859:Hydrogen / Q000378:metabolism*; D006864:Hydrogenase / Q000737:chemistry* / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000737:chemistry* / Q000378:metabolism*; D063747:Methanocaldococcus / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D011789:Quantum Theory
chemical_list: D007506:Iron-Sulfur Proteins; D006859:Hydrogen; C118830:iron hydrogenase; D006864:Hydrogenase
keywords: [Fe] hydrogenase; hydrogen activation; molecular mechanics; multiscale modeling; quantum mechanics