Author: Mumtaj Peer Mohammed (a*) &(a) , Aysha (a) and Dhamotharan(b) - 10/08/13, 11:56

More docking results of Mumtaj Peer Mohammed (a*) &(a) , Aysha (a) and Dhamotharan(b) Address: (a*)Corresponding author, (a) Heads of Departments of Bioinformatics & Microbiology, Mohamed Sathak College of Arts & Science, Chennai - 600 119, India.(b) Associate Professor, Department of Plant Biotechnology, Presidency College, Chennai - 600 005, India

Abstract: The study aimed at docking of TEM & modeled CTX - M by methanol extracted
compounds from Andrographis paniculata and to predict their binding efficiency.
BLAST-P was performed to retrieve suitable templates for homology-modeling using the blaCTX-M sequences obtained from Genbank .Protein Data Bank (PDB) IDs of these templates were retrieved. Models were prepared using Swiss-Model-Server and verified by Procheck and verify3D programmes RAMPAGE was used to prepare Ramachandran plots.
The 13 - Hexyl - oxa - cyclotridec - 10 - En- 2 - one was selected as ligand for this docking study from the data generated by Mass spectrometry analysis of methanol extracted compounds from Andrographis paniculata .The structure was drawn manually with aid of JME and its drug likeliness & molecular properties were calculated using Pre admet server.
Docking was performed by using docking server. Since the docking results proved that the amino acid residues Ser70,Ser 130,Ser237,Arg 276 and Thr235 of CTX-M-15 (enzyme) make important contacts with the ligand, researchers are expected to duly utilize this information for designing more potent and CTX - M inhibitors.

Docking calculations were carried out using DockingServer (Bikadi, Hazai, 2009). The MMFF94 force field (Halgren, 1998) was used for energy minimization of ligand molecule (From Corina 7941) using DockingServer. PM6 semiempirical charges calcuted by MOPAC2009 (J. P. Stewart, Computer code MOPAC2009, Stewart Computational Chemistry, 2009) were added to the ligand atoms. Non-polar hydrogen atoms were merged, and rotatable bonds were defined.
Docking calculations were carried out on CTX -M protein model. Essential hydrogen atoms, Kollman united atom type charges, and solvation parameters were added with the aid of AutoDock tools (Morris, Goodsell et al., 1998). Affinity (grid) maps of 20×20×20 Å grid points and 0.375 Å spacing were generated using the Autogrid program (Morris, Goodsell et al., 1998). AutoDock parameter set- and distance-dependent dielectric functions were used in the calculation of the van der Waals and the electrostatic terms, respectively.
Docking simulations were performed using the Lamarckian genetic algorithm (LGA) and the Solis & Wets local search method (Solis and Wets, 1981). Initial position, orientation, and torsions of the ligand molecules were set randomly. Each docking experiment was derived from 10 different runs that were set to terminate after a maximum of 250000 energy evaluations. The population size was set to 150. During the search, a translational step of 0.2 Å, and quaternion and torsion steps of 5 were applied.





















Docking calculations were carried out using DockingServer (Bikadi, Hazai, 2009). The MMFF94 force field (Halgren, 1998) was used for energy minimization of ligand molecule (From Corina 7941) using DockingServer. PM6 semiempirical charges calcuted by MOPAC2009 (J. P. Stewart, Computer code MOPAC2009, Stewart Computational Chemistry, 2009) were added to the ligand atoms. Non-polar hydrogen atoms were merged, and rotatable bonds were defined.
Docking calculations were carried out on CTX -M protein model. Essential hydrogen atoms, Kollman united atom type charges, and solvation parameters were added with the aid of AutoDock tools (Morris, Goodsell et al., 1998). Affinity (grid) maps of 20×20×20 Å grid points and 0.375 Å spacing were generated using the Autogrid program (Morris, Goodsell et al., 1998). AutoDock parameter set- and distance-dependent dielectric functions were used in the calculation of the van der Waals and the electrostatic terms, respectively.
Docking simulations were performed using the Lamarckian genetic algorithm (LGA) and the Solis & Wets local search method (Solis and Wets, 1981). Initial position, orientation, and torsions of the ligand molecules were set randomly. Each docking experiment was derived from 10 different runs that were set to terminate after a maximum of 250000 energy evaluations. The population size was set to 150. During the search, a translational step of 0.2 Å, and quaternion and torsion steps of 5 were applied.

Created with DockingServer

DockingServer Reference

• Bikadi, Z., Hazai, E.,
  Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock
  J. Cheminf. 1, 15 (2009)