Computational Ligand-Protein Docking Sample Clauses

Computational Ligand-Protein Docking. Glide Docking. Previously established “NAMFIS” conformations of PTX [44] were docked separately into the cavity regions of the human MD-2 crystal structure (PDB code 2E59)[38] devoid of lipid IVa and the mMD-2 homology model described above using Glide with SP precision (Schrödinger, LLC). This methodology regards the structure of the protein as a rigid body, but treats the ligand as a conformationally flexible molecule. The same PTX conformers were similarly docked into the ligand-free MD-2 X-ray structures derived from the hybrid-TLR4-hMD-2-Eritoran complex (PDB code 2Z65) and the mTLR4-mMD-2 complex (PDB code 2Z64).[39] Unlike the binding of PTX to β-tubulin,[13] neither MD-2 docking exercise led to NAMFIS conformations as the favored binding pose. Glide was also used to examine the relative energies of PTX docked to the external surfaces of the MD-2 proteins. Induced fit docking. To improve the fit between protein interior and PTX and to achieve deeper residence of the ligand within the cavity, induced fit docking with Prime v1.6 (Schrödinger, LLC) was performed. This approach allows both protein side chain movement and ligand flexibility. Duplicate poses were removed with MacroModel (Schrödinger, LLC), and the resulting MD-2/PTX complexes were sorted energetically with the MMGBSA scoring algorithm.[45]