Novel Natural Inhibitors Targeting AKT1 by Computational Study
Abstract Object: This study was designed to screen ideal lead compounds and drug candidates with an inhibitory effect on AKT1 from the drug library (ZINC database).Methods: A battery of computer-aided virtual techniques were used to identify potential inhibitors of AKT1. LibDock is used for structure-based screening followed by ADME (absorption distribution, metabolic excretion) and toxicity prediction. Molecular dynamics simulations were used to evaluate the stability of ligand-receptor complexes.Results: Two new natural compounds ZINC000049872065 and ZINC000021992902 were found to bind to AKT1 in the ZINC database, showing a higher binding affinity. Also, they were predicted to have lower rodent carcinogenicity, Ames mutagenicity, developmental toxicity potential, and high tolerance to cytochrome P4502D6. Molecular dynamics simulation shows that ZINC000049872065 and ZINC000021992902 have more favorable potential energies with AKT1, which can exist stably in the natural environment.Conclusion: This study suggests that ZINC000049872065 and ZINC000021992902 are ideal potential inhibitors of AKT1 targeting. These compounds are safe drug candidates and have important implications for the design and improvement of C-MET target drugs.