Grid Potential Analysis and Docking Studies on a Dataset of N-Arylsulfonyl-3-AcetylIndoles as Anti-HIV Agent

A grid potential analysis employing the AutoGPA module in MOE2009.10 was performed on a dataset of 42 molecules of N-arylsulfonyl-3-acetylindoles as anti-HIV agent. The molecular docking simulations were also employed to position the inhibitors to their binding site to determine the most appropriate binding mode for different conformations of molecule. The uniqueness of AutoGPA module is that it automatically builds the 3D-QSAR model on the pharmacophore based molecular alignment. The best AutoGPA 3D-QSAR model obtained in the present study gives the cross-validated q2 value of 0.588 and r2pred value of 0.701 among the fifty six 3D-QSAR model developed. Furthermore, the steric and electrostatic contour maps for AutoGPA model along with the 3D structure of protein (binding residue of active site) inlaid were obtained to better understand the structural requirements against HIV and interaction between binding residues of protein and inhibitors. The study shows that hydrophobic and hydrogen bonding potential groups are favorable for optimization of parent nucleus for better activity