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Updated: Jan 12, 2026
Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
An investigation of fucoidan as a potential inhibitor against DENV/NS3 proteases through molecular dynamics
Swaminathan Ramalingam1, Anuradha Venkatraman2, Sankar Muthumanickam3
1PG & Research Department of Biotechnology, Mohamed Sathak College of Arts and Science, Sholinganallur, Chennai, 600119, India.
Introduction:
Dengue virus (DENV) is a mosquito-borne disease that spreads in the tropics and subtropics mainly by the Aedes aegypti mosquito, infecting more than 100 million people every year and causing copious deaths every year. As of now, no direct-acting antiviral drugs or vaccines are available to combat DENV. Therefore, the identification of novel small molecules from natural origin becomes inevitable for the management of DENV fever. Here, fucoidan from Padina gymnospora was analyzed for competitive binding within the active site of nonstructural protein NS3 proteases selected as a potential therapeutic target for direct-acting antivirals.
Methodology:
The 3D structure of fucoidan was retrieved from Pubchem and molecular targets was fetched from the Protein Data Bank. Molecular docking was performed with Glide module of Schrodinger and molecular dynamics was studied using GROMACS software. Further, density functional theory (DFT) analysis, ADME properties, and BOILED-egg plot analysis were also studied. RESULTS AND DISCUSSION: The fucoidan compound was docked with the active site of NS3 proteases, showing docking score variation between -6.458 and -7.483 kcal/mol and strong interaction with the catalytic dyad His51, Asp75, and Ser135 amino acids. Furthermore, binding free energy was calculated by using prime MM/GBSA to assess the binding affinity of fucoidan towards the target protein. Moreover, molecular dynamics simulation was performed to evaluate the structural stability of the docked complexes. In addition, the small HOMO-LUMO gap of -0.189 eV given by DFT analysis indicated the structural stability between the ligand and the protein. The fucoidan phytocompound has satisfied all the relevant pharmacokinetic properties and is also highly absorbed by the gastrointestinal tract.
Conclusion:
From the overall findings of this study, it is concluded that the fucoidan from Padina gymnospora has effectively blocked the catalytic dyad of NS3 proteases, which could be considered a potent inhibitor to control the DENV multiplication infection.
