Applications of the Newly Developed Force-Field Parameters Uncover a Dynamic Nature of Ω-Loop C in the Lys-Ligated Alkaline Form of Cytochrome c .

Autor: Deng Y; Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, United States., Carnevale V; Institute for Genomics and Evolutionary Medicine, Institute for Computational Molecular Science, and Department of Biology, Temple University, Philadelphia, Pennsylvania 19122, United States., Ditchfield R; Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, United States., Pletneva EV; Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, United States.
Jazyk: angličtina
Zdroj: The journal of physical chemistry. B [J Phys Chem B] 2024 Jun 27; Vol. 128 (25), pp. 5935-5949. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1021/acs.jpcb.4c00625
Abstrakt: Lys-ligated cytochromes make up an emerging family of heme proteins. Density functional theory calculations on the amine/imidazole-ligated c -type ferric heme were employed to develop force-field parameters for molecular dynamics (MD) simulations of structural and dynamic features of these proteins. The new force-field parameters were applied to the alkaline form of yeast iso -1 cytochrome c to rationalize discrepancies resulting from distinct experimental conditions in prior structural studies and to provide insights into the mechanisms of the alkaline transition. Our simulations have revealed the dynamic nature of Ω-loop C in the Lys-ligated protein and its unfolding in the Lys-ligated conformer having this loop in the same position as in the native Met-ligated protein. The proximity of Tyr67 or Tyr74 to the Lys ligand of ferric heme iron suggests a possible mechanism of the backward alkaline transition where a proton donor Tyr assists in Lys dissociation. The developed force-field parameters will be useful in structural and dynamic characterization of other native or engineered Lys-ligated heme proteins.
Databáze: MEDLINE
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