Identification of a natural specific inhibitor for Akt۱ protein through molecular docking studies and evaluation of DFT calculations and molecular dynamics simulations

The protein kinase B (Akt۱) is a pivotal component in cellular signaling pathways and the regulation of cancer-related processes, establishing it as a vital target for the development of innovative therapeutic agents. This research examines natural inhibitors, including quercetin, resveratrol, and zingiberene, to assess their interactions with Akt۱ using molecular docking and free energy calculations density functional theory (DFT). Molecular docking analysis indicated that all three compounds possess the ability to bind to Akt۱'s allosteric site, with quercetin displaying the strongest interaction due to its lower binding energy and more stable hydrogen bonding. Detailed evaluation of van der Waals and electrostatic forces through DFT calculations identified these factors as critical to the stability of the complexes. Although resveratrol and zingiberene also demonstrated significant interactions with Akt۱, their binding energies and complex stabilities were comparatively weaker than those of quercetin. These findings suggest that quercetin holds substantial promise as a natural inhibitor for Akt۱ and could serve as a cornerstone for developing anticancer therapies derived from natural compounds. This study not only emphasizes the therapeutic potential of quercetin but also highlights the indispensable role of molecular modeling and DFT calculations in elucidating protein-ligand interactions. These discoveries provide a foundation for subsequent experimental research and practical innovations in drug design.

کلیدواژه ها:

AKT۱ ، quercetin ، resveratrol ، zingiberene ، molecular docking ، DFT