Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico...

The cyclin Ds-CDKs axis (Cyclophilin A (Cyp /Ganoderiol F)) plays a critical role in cancer through various processes, such as controlling proliferation and inhibiting cancer cells. Ganoderiol F derivatives can serve as oncogenic targets for multiple cancer types. This study demonstrated that the structure-guided design and development of novel Cyp A inhibitors and Ganoderiol F derivatives can be employed to select calculated positions for increased effectiveness in chemical inhibitors and their interaction with the chosen receptors. For this approach, numerous software applications were utilized to achieve optimal molecular interactions. Overall, 117 novel cyclophilin inhibitor ligand molecules were constructed using Chemsketch software. The converted PDB files of the novel Cyp A inhibitor ligands were prepared for introduction to the Sanglifehrin A enzyme receptor. Ligand-protein docking interactions were performed using AutoDock 4.2.6 software to reveal the best geometric interactions. The docking confirmations were carried out using PyMOL 2.5 software. Finally, hydrogen bonds were detected using Chimera and Maestro software. The selected ligand-receptor docked complex was subjected to molecular dynamics simulation. The MD simulation process demonstrated the stability of the complex and indicated that the chosen ligand can be utilized as a drug inhibitor for cancer cells. In the results, the active amino acids in binding site were identified as Arginine 55 that in motion of 1.53Å, Asparagine (Asn), Glycine (Gly), Threonine (Thr), Lysine (Lys), Isoleucine (Iso), Histidine (Hid), Phenylalanine (Phe), and Cysteine (Cys) with the highest number of hydrogen bond ligand of 45 hydroxymangiferonic. That connected with 1nmk receptor in grid box coordinate of X 38.86, Y of 10.987, and Z of 40.734. The 1nmk receptor-ligand complex evaluation in molecular dynamics (MD) simulation in Gromacs version CHARMM 36 force field has optimum degrees.