Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Vitalis Mbayo, Penny Poomani Govender, Ephraim Felix Marondedze, Krishna K. Govender · Journal of Visualized Experiments · 2025
of 0.815, indicating a high level of predictive accuracy. MDS were conducted to assess the stability of various ligands and their newly developed alternatives, ensuring they remained bound to the protein's active site over a 200-nanosecond simulation timeframe. Etravirine exhibited root mean square deviation (RMSD) fluctuations of approximately 4.5 Å, while its enumerated derivatives showed RMSD fluctuations of 3.5 Å. Through molecular docking, MDS, and free energy computations, enumerated Etravirine demonstrated the best performance, with an activity value of 7.373 and a docking score of -10.517 kcal/mol. Furthermore, the calculated free energy of binding for enumerated Etravirine was -89.684 kcal/mol, outperforming other ligands under investigation. The significant improvement suggests that the modified Etravirine holds promising potential as a novel agent in antiretroviral therapy. The obtained lower RMSD value, the enhanced amino acid interactions, and the highest binding free energy indicate that enumerated Etravirine could serve as a viable alternative for HIV/AIDS treatment.