title: 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.
authors.forename: Christo Z
authors.initials: CZ
authors.lastname: Christov
authors.forename: Alessio
authors.initials: A
authors.lastname: Lodola
authors.forename: Tatyana G
authors.initials: TG
authors.lastname: Karabencheva-Christova
authors.forename: Shunzhou
authors.initials: S
authors.lastname: Wan
authors.forename: Peter V
authors.initials: PV
authors.lastname: Coveney
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mulholland
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D051545:Cyclooxygenase 1 / Q000737:chemistry*; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D019563:Mechanics; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011789:Quantum Theory; D014443:Tyrosine / Q000737:chemistry
chemical_list: D016718:Arachidonic Acid; D014443:Tyrosine; D006859:Hydrogen; D051545:Cyclooxygenase 1