Steered Molecular Dynamics Simulations of Coumarin2 5Z/5E Pulling Reveal Different Interaction Profiles for Four Human Cytosolic Carbonic Anhydrases

Authors : Mustafa TEKPINAR

Pages : 406-415

Doi:10.19113/sdufbed.47662

View : 27 | Download : 7

Publication Date : 2018-08-15

Article Type : Research Paper

Abstract :Carbonic anhydrase insert ignore into journalissuearticles values(CA); is an important enzyme, which has multiple isoforms each performing different functions in humans. Characterizing the interactions of carbonic anhydrase isoforms with ligands is a difficult but important task. In recent years, steered molecular dynamics insert ignore into journalissuearticles values(SMD); has been used successfully to characterize ligand binding and unbinding events. In this study, constant velocity SMD simulations were performed on four cytosolic human carbonic anhydrases insert ignore into journalissuearticles values(carbonic anhydrase I, II, III and VII); using a ligand called Coumarin2 5Z/5E to understand better the nature of interactions between this ligand and the various enzyme isoforms. The influence of force constant and pulling velocity on SMD simulations were investigated. When the force constant and the pulling velocity were changed, no significant effect on interaction profiles was observed. Finally, hydrogen bond interactions, Histidine 64 positions and the differences between force-distance profiles for all isozymes were analyzed. These results demonstrate that human cytosolic carbonic anhydrases I, III, and VII show similar Coumarin2 5Z/5E unbinding patterns with different rupture forces, while carbonic anhydrase II has a distinct interaction profile.
Keywords : Steered molecular dynamics, Coumarins, Rupture force, Protein ligand interaction, Human cytosolic carbonic anhydrases