Molecular Docking of TPI Proteins

Small molecules were built in Sybyl (Certara Corp.) and saved in mol2 format. The two TPI protein receptors from Trypanosoma cruzi (PDB code 1tcd) and S. cerevisiae (1ypi) were prepared in Sybyl using the protein preparation tools to add hydrogens, properly type atoms, and remove any clashes. AutoDock Tools^{86 (link)} were used to prepare the ligand and receptor pdbqt files and to select the docking box size for Autodock4. The docking box size was large enough to include the dimer interface described by Kurkcuoglu et al.^{50 (link)}. Autodock4.2.6 was run with Lamarkian Genetic Algorithm, with 25 M energy evaluations for 27,000 generations. This method includes a Solis & Wets local search of the ligand in the receptor after docking. Autodock 4.2.6 calculates a binding energy by summation of the molecular energy components (vdw + Hbonding + desolvation + electrostatics + ligand torsional free energy) minus the unbound system energy. The 30 best-docked ligands were examined. Optimal docking results were displayed in Pymol (PyMOL Mol. Graphics System, Ver. 1.8.2, Schrodinger, LLC).