Insights into novel inhibitory compounds against 14–3-3 ε potential cancer therapeutic target through microscopic solvated dynamics

Signal transduction, protein trafficking, cell cycle, and apoptosis are some examples of intracellular signaling pathways controlled by 14–3–3 proteins. Although 14–3–3 proteins have roles in numerous illnesses in humans, notably cancer, neurodegeneration, and reproductive problems, they are important options for drug targets. To effectively manage 14–3–3 ε protein, we have tested drug-like compounds in this study for protein inhibition. The Comprehensive Marine Natural Products Database (CMNPD) has 47,451 compounds and a Seaweed library, 1077 compounds underwent structure-based virtual screening. It’s important to note that molecular docking studies suggest the compounds BC005, BC010, and CMNPD164 have strong binding affinities with a binding score of (−8.2 kcal/mol), (−7.8 kcal/mol), and (−7.3 kcal/mol) respectively. In addition, the results of molecular dynamics indicated that the compounds screened were found to be stable and to stay in the binding sites for the duration of the 100-ns run. The measured pharmacokinetic features were within the allowed range and the compounds were considered drug-like and fell under Lipinski Rule 5. Throughout the simulation, Molecular Mechanics Poisson–Boltzmann Surface Area (MMPBSA), water swap energy estimation, and entropy calculations were carried out. The salt bridge studies and secondary structure analysis suggested how inhibitory action changes the secondary structural elements of protein as well as how salt bridges maintain protein–ligand complexes intact. Therefore, we believe that compounds BC005, BC010, and CMNPD164 might inhibit14-3–3 ε and be helpful as potential drugs for the treatment of cancer-based on the findings of molecular docking and dynamic simulations.