5. Molecular docking ligand and binding energy interaction sesquiterpenoid/sesquiterpenoid alcohols to protein COX-1 and COX-2

We used Hex8.0 software (http://hex.loria.fr) for rigid docking to compute possible interaction COX-1 and COX-2 with (alpha-bulnesene (CID94275), alphaguaiene (CID107152), seychellene (CID519743) and sesquiterpenoid alcohols such as alpha-Patchouli alcohol isomers (CID442384, CID521903, CID6432585, CID3080622, CID10955174, and CID56928117) on the interaction site. Output of the docking was refined using Discovery Studio Client 3.5 software. We used Discovery Studio Client 3.5 to perform interactions, ligand binds to COX-1/COX-2 and Ramachandran plot analysis.

The repeat rigid docking used Hex 8.0 software to compute possible interaction COX-1 and COX-2 with sesquiterpenoid/sesquiterpenoid alcohols such as alphabulnesene (CID94275), alpha-guaiene, seychellene (CID519743), and alphapatchouli alcohol isomers (CID442384, CID521903, CID6432585, CID3080622, CID10955174, and CID56928117) on its interaction site and the data are represented by Discovery Studio 3.5 software in (Figure 5(a1–l1)). The interaction site position of COX-1/COX-2-sesquiterpenoid/sesquiterpenoid alcohol complexes were analyzed using Discovery Studio-3.5 Client software to get the receptor-ligand interaction and Ramachandran plot, as shown in Figure 5; some of them are alphapatchouli alcohol isomers-COX-1/COX-2 complexes.

In Table 2 and Figure 6, the interactions active site of ligand sesquiterpenoid/ sesquiterpenoid alcohol with COX-1 and COX-2 protein receptor showed the differences in the position active site. The different positions were analyzed and presented in the Ramachandran plot analysis and its amino acid residues in the receptor active site of COX-1 and COX-2 in which hydrogen atoms and hydroxyl groups on each of the 3D-isomers of alpha-patchouli alcohol structure were in different position (Figure 4). The results of docking and analysis of the active site also show that all ligands sesquiterpenoid/sesquiterpenoid alcohol are in the catalytic domain. Thus, all the compounds have the capability of blocking oxygenated reaction and reaction peroxides; currently substrate arachidonic acid becomes PGH2.

Each ligand, CID521903, was seen interacting with HEM682B group in COX-2- CID521903 complexes. This result proved that it would lead to inhibition of enzymatic reactions occurring COX-1 and COX-2. The analysis of active site showed that there are any difference and similarities of the active site of all ligand alphapatchouli alcohol isomers which is interact with receptor proteins COX-1 and COX-2. This difference is caused by different stereoisomers of hydrogen atoms and hydroxyl group in alpha-patchouli alcohol isomers. The different position active site the complexes have led to interaction types, such as hydrogen bond, van der Waals, electrostatic and covalent bond. The different types of interactions in this complex will certainly affect its binding free energy.

2D-sesquiterpernoid/sesquiterpenoid alcohol, such as alpha-bulnesene (CID94275),

CID56928117) show the different position of hydroxyl group and hydrogen atom. The 3D structure of sesquiterpenoid/sesquiterpenoid alcohol was retrieved in 3D-SDF format from http://pubchem.ncbi.nlm.nih.gov/. For the preparation of docking, 3D-SDF format of isomers was converted to 3D-PDB using open babel software. This program helps to search, convert, analyze, or store data which has a wide range of applications in the different fields of molecular modeling, computational chemistry, and so forth. For a common user, it helps to apply chemistry aspects without worrying about the low level details of chemical information. It also converts crystallographic file formats (CIF, ShelX), reaction formats (MDLRXN), molecular dynamics and docking (AutoDock, Amber), 3D viewers (Chem3D, Molden), and chemical kinetics and thermodynamics (ChemKin, Termo) [6, 8].

3D model from PDB ID: 1PTH was obtained from SWISS-MODEL repository for cyclooxygenase-1 (COX-1) (http://www.rcsb.org/pdb/explore/explore.do?structure Id=1pth) and 3D model from PDB ID: 6COX for cyclooxygenase-2 (COX-2) [6, 8].

In Figure 5 shows the Ramachandran plot analysis of COX-1 and COX-2 protein receptor before rigid docking. It showed that COX-1 protein receptor had 97.5% favored regions, 2.4% allowed regions, and, 0.2% outlier regions. Whereas, COX-2 protein receptor had 81.9% favored regions, 15.4% allowed regions and 2.7% outlier regions. Ramachandran plot displays the main chain torsion angles phi, psi (φ, Ψ) (Ramachandran angles) in a protein of known structure. The model was verified to guarantee the validity of programming and algorithms implemented. Results of the validity test showed that amino acid residues were distributed at the most favorable region in the Ramachandran plot. This is an indication of the stereochemical quality

alpha-guaiene, and seychellene (CID519743), and alpha-Patchouli isomers (CID442384, CID521903, CID6432585, CID3080622, CID10955174, and

Molecular Docking and Molecular Dynamics

4. Cyclooxygenase protein receptor (COX-1 and COX-2)

Figure 5.

48

Ramachandran plot analysis of COX-1 and COX-2.

We used Ramachandran plot analysis for validation protein receptor [32].


Table 2.

Analysis of virtual modeling of COX-1/COX-2-sesquiterpenoid/sesquiterpenoid alcohol complexes.
