Paper Title
3D MODELING OFN-ACETYL-ALPHA-NEURAMINIDASE 3 (NEU3) AND ITS STRUCTURAL INSIGHT

Abstract
Abstract - 3D modeling of N-acetyl-alpha-neuraminidase 3 (NEU3) was performed for the development of anticancer drugs.A software package the Molecular Operating Environment was utilized and structural analysis and docking simulations of the enzyme was also performed. As a template, a human NEU2 (PDB code: 1SNT) was chosen for the modeling of the 3D structure of NEU3. The structural justification of the modeledNEU3was achieved by the superimposition and root mean square deviation analysis, which exhibited significant 2D and 3D similarities of the modeled NEU3 to the template NEU2. However, the modeled NEU3 showed dissimilarity to the template NEU2 at the ligand binding site (LBS) in the molecular electrostatic potential (MEP) map, which revealed that the NEU3 model was different from the NEU2 model particularly at the LBS electrostatically. Furthermore, similarity of the ligand-receptor bound location and dissimilarity of binding orientations were found between the NEU2 and the NEU3 models by docking simulations. The difference in MEP maps was ascertained by the different binding orientations between the N-acetyl-2, 3-dehydro-2-deoxyneuraminic acid (DANA)-NEU2 and DANA-NEU3 (DANA is a known inhibitor of NEUs). Docking simulations also showed that DANA could interact with a catalytically important amino acid residue Arg25 but not with the other 4 residues that are considered crucial for the reaction of the enzyme. These results suggest that the 3D modeling of NEU3 was performed successfully and docking simulations could be utilized for elucidating important ligand-receptor interactions between inhibitors and NEU3 for application to target NEU3 for the development of anticancer drugs. Keywords - N-Acetyl-Alpha-Neuraminidase 3 (NEU3), Cancer, Docking Simulation, In Silico, 3D Modeling