Estimation of the Binding Affinities of Glycogen Phosphorylase Inhibitors by Molecular Docking to Support the Treatment of Type 2 Diabetes

Document Type : Regular Article

Authors

1 Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam

2 Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam

3 NTT Hi-Tech Institute, Nguyen Tat Thanh University, HCMC, Vietnam

10.22036/pcr.2024.422780.2440

Abstract

In the current landscape of drug discovery, various docking programs for virtual database screening significantly reduce costs and time. This study re-docked twenty-three inhibitors of glycogen phosphorylase (GP), a key target for type 2 diabetes (T2D) therapy, using seven methods including Autodock 4 (AD4), AutoDockVina (Vina), modified Vina (mVina), Standard Precision mode (SP) and Extra Precision mode (XP) of Glide methods, Molecular Operating Environment (MOE) and Genetic Optimization for Ligand Docking (GOLD). Results showed that GOLD showed the worst computational precision with the highest RMSE of 20.98 kcal.mol-1. Conversely, MOE was the most precise with the lowest RMSE of 1.99 kcal.mol-1, closely followed by AD4. However, MOE failed to generate the correct ligand-binding pose, showing a 0% success rate in docking for all RMSD resolutions (<0.2, 0.15, and 0.1 nm). Among the top-performing methods, GOLD surpassed others in docking success rates for GP ligands, achieving 96% at RMSD <0.2 nm, compared to 74%, 70%, and 74% for AD4, Vina, and mVina, respectively. These four packages can produce a ligand-binding posture that closely resembles the crystal structure discovered through experimental studies. The findings serve as the foundation for selecting an appropriate tool for screening candidate drugs for the T2D therapeutic target.

Graphical Abstract

Estimation of the Binding Affinities of Glycogen Phosphorylase Inhibitors by Molecular Docking to Support the Treatment of Type 2 Diabetes

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Physical Chemistry Research
Volume 12, Issue 3 - Serial Number 43
September 2024
Pages 821-835

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History

  • Receive Date: 29 October 2023
  • Revise Date: 15 December 2023
  • Accept Date: 29 January 2024

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