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Conformational effects on the pro-S hydrogen abstraction reaction in cyclooxygenase-1: an integrated QM/MM and MD study.

ABSTRACT: A key step in the cyclooxygenase reaction cycle of cyclooxygenase 1 (COX-1) is abstraction of the pro-S hydrogen atom of the arachidonic acid by a radical that is formed at the protein residue Tyr-385. Here we investigate this reaction step by a quantum-mechanics/molecular-mechanics approach in combination with molecular-dynamics simulations. The simulations identify the hydrogen abstraction angle as a crucial geometric determinant of the reaction, thus revealing the importance of the cyclooxygenase active site for calculating the potential energy surface of the reaction.

SUBMITTER: Christov CZ

PROVIDER: S-EPMC3870816 | biostudies-other | 2013 Mar

REPOSITORIES: biostudies-other

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Conformational effects on the pro-S hydrogen abstraction reaction in cyclooxygenase-1: an integrated QM/MM and MD study.

Christov Christo Z CZ Lodola Alessio A Karabencheva-Christova Tatyana G TG Wan Shunzhou S Coveney Peter V PV Mulholland Adrian J AJ

Biophysical journal 20130301 5

A key step in the cyclooxygenase reaction cycle of cyclooxygenase 1 (COX-1) is abstraction of the pro-S hydrogen atom of the arachidonic acid by a radical that is formed at the protein residue Tyr-385. Here we investigate this reaction step by a quantum-mechanics/molecular-mechanics approach in combination with molecular-dynamics simulations. The simulations identify the hydrogen abstraction angle as a crucial geometric determinant of the reaction, thus revealing the importance of the cyclooxyge ...[more]

PMID: 23473504

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