Effect of Single-Point Mutations on Nitric Oxide Rebinding and the Thermodynamic Stability of Myoglobin

Diamantis, Polydefkis and El Hage, Krystel and Meuwly, Markus. (2019) Effect of Single-Point Mutations on Nitric Oxide Rebinding and the Thermodynamic Stability of Myoglobin. The Journal of Physical Chemistry B, 123 (9). pp. 1961-1972.

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Official URL: https://edoc.unibas.ch/75023/

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The effect of single amino acid mutations on the rebinding dynamics of nitrogen monoxide (NO) to myoglobin is investigated using reactive molecular dynamics simulations. In particular, mutations of residues surrounding the heme-active site (Leu29, His64, Val68) were considered. Consistent with experiments, all mutations studied here have a significant effect on the kinetics of the NO-rebinding process, which consists of a rapid (several 10 ps) and a slow (100s of ps) time scale. For all modifications considered, the time scales and rebinding fractions agree to within a few percents with results from experiments by adjusting one single, physically meaningful, conformationally averaged quantity: the asymptotic energy separation between the NO-bound (2A) and photodissociated (4A) states. It is furthermore shown that the thermodynamic stability of wild-type versus mutant Mb for the ligand-free and ligand-bound variants of the protein can be described by the same computational model. Therefore, ligand kinetics and thermodynamics are related in a direct fashion akin to Φ-value analysis, which establishes a relationship between protein folding rates and thermal stability of proteins.
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Physikalische Chemie (Meuwly)
UniBasel Contributors:Meuwly, Markus
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
Note:Publication type according to Uni Basel Research Database: Journal article
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edoc DOI:
Last Modified:30 Jun 2020 13:45
Deposited On:21 Feb 2020 11:55

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