Abstract
The monotopic proteins COXβ1 and β2 in dimeric form bound to lipid bilayer membranes are studied using molecular dynamics simulations within an aqueous environment. The 25βns simulations are performed for both isozymes with arachidonic acid bound in the cyclooxygenase sites. The interactions between the enzymes and the lipids are analyzed, providing insight into the attachment mechanism of monotopic proteins to membranes. Our study reveals some key differences between the two isozymes that include the orientations at which they sit on the surface of the membranes and the depths to which they embed within the membranes. The differences in membrane association of the isozymes indicate that they may integrate distinctively with the same membrane, and/or with different membranes or their lipid components. Our results indicate that arachidonic acid can be bound in the cyclooxygenase active site in distinct catalytically competent conformations that lead to certain hydroperoxy acids; and the arachidonic acid and/or cyclooxygenase sites undergo a conformational change which makes only one subunit of each homodimer catalytically active. Β© 2008 Wiley Periodicals, Inc. J Comput Chem 2009