Discovery studio modeling environment v4

All applications in the
molecular docking simulation were provided in Maestro module of Schrödinger
Suite 2022-2.³⁰ The cryo-EM structure of
CFTR was obtained from protein data bank (PDB id: 6O2P),^{25 (link)} which was prepared with Protein Preparation Wizard. The
receptor grid was generated 20 × 20 × 20 Å space region
centered at the co-ligand of the complex structure, and then the low-energy
3D structures of Cact-3, 16d, and 16e were
docked with default values in SP mode using Glide module. Using the
structure of protein–ligand complex corresponding to the best
pose of Cact-3, 16d, and 16e, the protein
residues that have atoms within 3 Å of the ligand were refined
in the environment with an implicit membrane by Refine Protein–Ligand
Complex module. We calculated each binding energy of 16d/16e using the MM-GBSA method with Prime, where the implicit membrane
was also considered. The protein–ligand interactions were analyzed
by Discovery Studio Modeling Environment v4.026 (BIOVIA, San Diego,
CA, USA), and the docking models were displayed using PyMOL version
2.0.47.

All applications in the molecular docking simulation were provided in the Maestro module of Schrödinger Suite 2020-3. The X-ray crystal structure of the PARP-1/olaparib complex was acquired from the Protein Data Bank (PDB ID: 5DS3; ref. 24 (link)). The receptor grid was generated in a 20 × 20 × 20 Å space region centered at the coligand of the complex structure. Thereafter, energy-minimized three-dimensional structure of venadaparib was docked with default values in the SP mode using Glide. The protein–ligand interactions were analyzed using Discovery Studio Modeling Environment v4.026 (BIOVIA) and the docking models were displayed using PyMOL v2.0.47 (Schrödinger Suite).