molecular modeling of 3-(1,3-dioxoisoindolin-2-yl) benzyl nitrate and its molecular docking study with phosphodiesterase-5 (pde5)

In this study, the electronic properties of the novel medicinal compound 3-(1,3-dioxoisoindolin-2-yl) 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/6-311++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 phosphodiesterase-5 (pde5) enzyme. on the other hand, the docking analysis of the ligand-enzyme 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 ligand-enzyme complex formation.