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

Christo Christov, Alessio Lodola, Tatyana Karabencheva-Christova, Shunzhou Wan, Peter Coveney, Adrian Mulholland

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)L5-L7
JournalBiophysical Journal
Volume104
Issue number5
DOIs
Publication statusPublished - 5 Mar 2013

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