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

doi:10.1016/j.bpj.2013.01.040

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

Applied Sciences Department

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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 language	English
Pages (from-to)	L5-L7
Journal	Biophysical Journal
Volume	104
Issue number	5
DOIs	https://doi.org/10.1016/j.bpj.2013.01.040
Publication status	Published - 5 Mar 2013

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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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AU - Lodola, Alessio

AU - Karabencheva-Christova, Tatyana

AU - Wan, Shunzhou

AU - Coveney, Peter

AU - Mulholland, Adrian

PY - 2013/3/5

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N2 - 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.

AB - 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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DO - 10.1016/j.bpj.2013.01.040

M3 - Article

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SP - L5-L7

JO - Biophysical Journal

JF - Biophysical Journal

IS - 5

ER -

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

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