Computational protocol: Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

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Protocol publication

[…] The molecular docking study was carried out with AutoDock 4.2 with AutoDockTools 1.5.6 extension. Dockings were performed with the ligands dichotomanol, pachydictyol A, and isopachydictyol constructed in the Spartan program and the human Alpha thrombin, available on PDB with the entry code 1PPB. The protein and the ligands were prepared by the addition of hydrogens atoms, Gasteiger partial atomic charge calculation, polar hydrogen graphic analyses, and Ad4 program file atoms definition. The maximum allowed conformation number was defined in the active site.The cubic grid box was set to 60 × 60 × 60 points with a spacing of 0.375 Å containing the main residues of catalytic site, loop-60 and γ-loop regions, Na+ binding site, and ABEI or ABEII. In case of the catalytic site the grid box were centralized using the following coordinates (x = 3.178; y = 21.109; z = 15.649). To find the best orientations and conformations of the ligands in the protein binding sites the Lamarckian Genetic algorithm was selected, with an initial population size of 150, a maximum number of evaluations of 2.5 × 106 (medium), maximum number of generations of 27,000, gene mutation rate of 0.02, crossover rate of 0.8, and number of GA runs equal to 50.In order to confirm the efficiency of this methodology, docking performance and accuracy were validated by re-docking the inhibitor D-Phe-Pro-Arg Chloromethylketone in the human alpha-thrombin active site (PDB:1PPB). […]

Pipeline specifications

Software tools AutoDock, Spartan
Applications Drug design, Protein interaction analysis
Diseases Thrombosis
Chemicals Diterpenes