Electronic structure, vibrational assignments and simulation studies with A/T rich DNA duplex of an aromatic bis-amidine derivative

In this paper, computational investigations have been carried out on an aromatic bis-amidine which is considered to be crucial due to its peculiar properties including anti-Pneumocystis carinii pneumonia(PCP), anti-inflammatory and anticancer activities. The raw structure of an aromatic bis-amidine namely; 2,5-bis[4-(N-cyclohexyl-amidino)phenyl]furan was retrieved, optimized and geometrical parameters were computed. The computational results have been compared with those of reported experimental values. In order to check its binding capability, we pave the way a step further by the interaction of the molecule with DNA duplex, 5′(CGCGAATTCGCG)3′, which consisted of A/T base pairs in its central region. In addition to geometrical, MEP, HOMO-LUMO analyses and IR assignments, molecular docking with DNA has also been performed. The best docked complex was subjected to molecular dynamics simulation for 50 ns using AMBER force field. Free energy of binding has been calculated using MM/PBSA method. The outcomes demonstrate that the molecule recognizes both the strands of DNA duplex through hydrogen bonding within the minor groove side, preferably at A/T rich region and remains stable during the course of dynamics. It may be concluded that the compound shows better binding capability with duplex under study and may be used as a drug lead against Pneumocystis carinii pneumonia.