Integrative Study on the Binding Energy Calculation: Molecular Docking and Molecular Mechanics with Generalized Born Surface Area Targeting Acetylcholinesterase

Ignasius Widya Parahita Putranto (Magister of Pharmacy Study Program, Faculty of Pharmacy, Sanata Dharma University, Campus 3 Paingan, Maguwoharjo, Depok, Sleman, Yogyakarta 55282 Indonesia)
Bonifacius Ivan Wiranata (Pharmaceutical Sciences Department, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, Indonesia)
Enade Perdana Istyastono (Department of Pharmacy, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jl. Pluit Raya No. 2, Jakarta Utara, DKI Jakarta, 14440, Indonesia)
Florentinus Dika Octa Riswanto (Research Group of Computer-Aided Drug Design and Discovery of Bioactive Natural Products, Sanata Dharma University, Yogyakarta 55282, Indonesia)

Journal of Pharmascience
Vol. 13 No. 1 (2026): Jurnal Pharmascience

Alzheimer's disease (AD) imposes a significant global financial burden. Previous studies have reported that acetylcholinesterase (AChE) activity is strongly associated with AD, making it a key target in therapeutic research. Molecular docking and computational techniques are increasingly used to study these associations, yet a surge in publications has led to a departure from strictly designed paradigms. This study evaluates the accuracy of the Gibbs free energy of binding (ΔG) from molecular docking scores, Molecular Mechanics/Generalized Born Surface Area (MM/GBSA), and local Vina scores. The Spearman rank test was applied to compare ΔG predictions and the in vitro results from our previous study. The correlation coefficient for molecular docking was -0.491, the MM/GBSA correlation coefficient calculated at the best molecular docking pose was -0.309, the MM/GBSA correlation coefficient calculated at the last 5 nanoseconds (ns) snapshots was 0.164, and the correlation coefficient of the Vina local score calculated at the last 5 ns snapshots was 0.273. Our findings indicate that the ΔG prediction from the Vina local score for the last 5 ns shows the strongest correlation with in vitro results.