Molecular Modeling of 3(1,3Dioxoisoindolin2yl)benzyl Nitrate and its Molecular Docking Study with Phosphodiesterase5 (PDE5)

In this study, the electronic properties of the novel medicinal compound 3(1,3dioxoisoindolin2yl) benzyl nitrate as a treatment of sickle cell disease are obtained using density functional theory (DFT) method. In first step, the molecular structure of the title compound is optimized at B3LYP/6311++G(d,p) level of theory at room temperature. Then, its stability and reactivity properties are calculated by frontier molecular orbitals (FMOs) energies. The global reactivity indices show this medicinal molecule is a more stable compound and the nitrogen atom of the nitrate group has positive charge. So, the nitrate group can quit nitric oxide molecule in binding to Phosphodiesterase5 (PDE5) enzyme. On the other hand, the docking analysis of the ligandenzyme complex shows the steric interactions play the main role in this complex formation. Also, the data shows the PDE5 residues containing Phe [A] 820, Gln [A] 817, Ile [A] 768, Val [A] 782, Gln [A] 775, Phe [A] 786, Ile [A] 778, Leu [A] 765, Met [A] 816, Ala [A] 767 and Tyr [A] 612 play main role in the ligandenzyme complex formation.