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

Christov, Christo, Lodola, Alessio, Karabencheva-Christova, Tatyana, Wan, Shunzhou, Coveney, Peter and Mulholland, Adrian (2013) Conformational effects on the pro-S hydrogen abstraction reaction in cyclooxygenase-1: an integrated QM/MM and MD study. Biophysical Journal, 104 (5). L5-L7. ISSN 0006-3495

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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.

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