Structural and Dynamical Study of Bovine Carbonic Anhydrase II in the Presence of Substrate: An Essential Dynamics and Molecular Dynamics Simulation Study

Abstract

Activity, regulation and inhibition of Bovine Carbonic Anhydrase II (BCAII), like other enzymes, are associated with its conformational changes.Molecular dynamics simulation was performed for Free BCAII and BCAII in complex with Para-nitro phenyl acetate to investigate the effect of substrate binding on BCAII structure and dynamics. Each Simulation was done for 100ns, in water with GROMACS software package. DSSP and Essential Dynamics techniques were used for analyzing secondary structures and concentrated motions, respectively. Results of this study demonstrated that presence of Para-nitro phenyl acetate in BCAII active site increased RMSD in the secondary structure backbone resulting in increasing number of amino acids in alpha helix and beta sheet and as opposed to turns. Flexible regions are located in the N-terminal while, surface of the protein and its central domain and the c-terminal have low flexibility and high resistance against changes. Motions have been induced in protein surface and secondary structures. Reduced motion in several sites, including amino acids 52 to 58 and 173 to 175 was observed. Increased motion in several sites, including beta sheets and alpha helices was induced. Results are in good agreement with studies on BCAII knotted structure and resistance against conformational changes.