Investigation of Akt1 behavior on gold surface from molecular dynamics insight.

In the past few years, gold nanoparticles (AuNPs) have shown great roles in biomedical areas. They can interact with proteins and change their structure and function. The serine/threonine kinase AKT plays a key role in cellular processes. Therefore, the AKT protein is known as a drug target for cancer treatment. In this study, we assessed the effect of gold nanoparticles on the AKT1 protein using molecular docking and molecular dynamics simulation. The results show that the AKT1 protein binds to citrate-coated gold surface predominantly through electrostatic and hydrophobic interactions. The RMSF calculations show that the AKT1 protein in the presence of gold nanoparticles exhibits less dynamic than the free state. The presence of gold nanoparticles causes the protein to have less compactness. The linker domain in the inactive conformation, and the regulatory domain and the glycine-rich loop in the active conformation of the AKT1 protein have higher dynamics than other regions. Furthermore, free energy landscape calculations show that AKT1 protein has a more conformational entropy in complex states in two active and inactive conformations. The results show that gold nanoparticles can affect the AKT1 protein and as a result, inhibit the phosphorylation flow in the protein signaling pathway in cancer cells.