3d Pharamacophore Model, Virtual Screening, Binding Affinity and Molecular Dynamics Studies of Potential Anticancerous Compounds Against Mammalian Target Rapamycin

Breast cancer is a genetically-based public health issue that affects people worldwide. The advancement of the FKBP12-rapamycin complex of the mammalian target (mTOR), the protein that is dysregulated in breast cancer, is essentially concerned with a hormone receptor. The mTORC1 and mTORC2 multiprotein complexes may be cleaved by mTOR, a serine/threonine kinase. mTOR's fap receptor movement is deregulated, which plays a part in cancer, weight, and maturing. The current study aims to acquire anti-cancer compounds from Naturally occurring Plant-based Anti-cancer Compounds (NPACT) as ligands against the target proteins of human breast cancer and identify promising hits against each target protein by analyzing ADME/T (Absorption, Distribution, Metabolism, and Excretion) properties for the chosen ligands and biomolecular interactions. Analyzing the biomolecular interactions, a pharmacophore model with a structure-based was created. and validated using Maestro 11.1. The best three compounds obtained after high-throughput screening are fap-363127 (taiwanin C), 5490349 (20-hydroxyresiniferol 9,13,14-orthophenylacetate), and 493164 (taiwanin E). The pharmacophore model displayed three main features: ARRR, Hydrogen bond acceptor, donor, and aromatic rings. Molecular Dynamics (MD) is a computer simulation technique for examining the physical fluctuations of molecular complexes using GROMACS (GROningen MAchine for Chemical Simulations). The explicit solvent model simulated the protein-ligand complexes for 100 ns. The RMSD (Root Mean Square Deviation) value of the mTOR-Benzothiazol complex ranges between 0.2 nm and 3 nm. The RMSF (Root Mean Square Fluctuation) and Rg (Radiation of gyration) are done by the highest binding compounds. This study suggests that the selected chemicals should be researched and analyzed further for breast tumor treatment and care strategies.