Computational Characterization of N-acetylaspartylglutamate Synthetase: From the Protein Primary Sequence to Plausible Catalytic Mechanism

Авторы: Polyakov I.V., Kniga A.E., Nemukhin A.V.
Журнал: Supercomputing Frontiers and Innovations
Том: 9
Номер: 2
Год издания: 2022
Первая страница: 4
Последняя страница: 13
DOI: 10.14529/jsfi220201
Аннотация: The methods of supercomputer molecular modeling are applied to characterize structureand dynamics of one of the key human brain enzymes, N-acetylaspartylglutamate synthetase.The three-dimensional all-atom models of the enzyme with the reactants in the active site areconstructed in several steps, starting from pilot protein structure in the apo-form obtained with theAlphaFold2 from the protein primary sequence. Deposition of reactant molecules into the proteincavity, construction of the reaction intermediate and relaxation of the complex are carried outwith the help of large-scale classical molecular dynamics calculations. On the top of the construct,molecular dynamics simulations with the quantum mechanics/molecular mechanics interactionpotentials are performed for the most promising conformations of the model system. Analysis ofthe latter allows us to propose plausible catalytic mechanisms of chemical reactions in the enzymeactive site. The applied computational strategy opens the way towards ab initio enzymology usingmodern supercomputer simulations.
Добавил в систему: Немухин Александр Владимирович

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