Conformational Effects on the pro - S Hydrogen Abstraction Reaction in Cyclooxygenase-1: An Integrated QM/MM and MD Study
Christo Z. Christov, Alessio Lodola, Tatyana G. Karabencheva‐Christova, Shunzhou Wan, Peter V. Coveney, Adrian J. Mulholland · Biophysical Journal · 2013
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.