Programme

O.8 -- Oral, VCTP-46

Date: Monday, 4 October 2021

Time: 16:50 - 17:10

Estimating Potential Inhibitors for AChE and SARS-CoV-2 Main Protease using Machine Learning, Molecular Docking, and Molecular Dynamics Simulations

T. Ngoc Han Pham (1), Quynh Mai Thai (2), Thien-Y Vu (3), Son Tung Ngo (4)

(1), (2), (3) Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam (4) Laboratory of Theoretical and Computational Biophysics, Ton Duc Thang University, Ho Chi Minh City, Vietnam (4) Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam

Although traditional medicine and medicinal chemistry achieved a huge success, they require a lot of time and cost to develop a new therapy. In that context, computer-aided drug design (CADD) emerges as an effective and rapid tool for drug discoveries. In CADD, accurately determining the non-covalently chemical reactions between protein and ligand is the most important issue, which can be resolved via physical-based and knowledge-based approaches. In this work, molecular docking, fast pulling of ligand (FPL) simulations, and machine learning (ML) calculations were employed to estimate the potential inhibitors for AChE. In particular, ML was initially used to screen a large database of compounds. Autodock Vina (Vina) and Autodock4 (AD4) were then employed to estimate ligand-binding pose and affinity of ML top-lead compounds inhibiting AChE. Although AD4 indicates a more correlate ligand-binding affinity, Vina suggests a more accurate binding pose. FPL, is non-equilibrium dynamics stimulation using an external force as an inverse problem to find out how a ligand dissociation to a protein, was finally used to validate the docking results. Cassiamin A and B probably play as potential inhibitors for Alzheimers prevention. Besides, using a combination of molecular docking and FPL simulations, periandrin V, penimocycline, cis-p-Coumaroylcorosolic acid, glycyrrhizin, and uralsaponin B were suggested that are possible inhibitors for SARS-COV-2 main protease (3CL or Mpro). Although the computational approaches were rigorously applied, further experiments should be carried out to refine the obtained results.

Presenter: Pham Thi Ngoc Han