Structural dynamics of influenza A (H1N1) hemagglutinin protein: a comparative study of Indian (2018) isolate with...

Area of Science:

• Virology
• Structural Biology
• Computational Biology

Background:

• H1N1 influenza virus HA proteins are crucial for viral entry.
• Mutations in HA can alter viral properties and host interactions.
• Understanding HA structure-dynamics is key to antiviral development.

Purpose of the Study:

• To compare the structure and dynamics of two H1N1 HA trimers: pandemic Californian (HA_Cal) and mutant Indian (HA_Ind).
• To investigate the impact of mutations on HA stability, dynamics, and potential viral-host interactions.

Main Methods:

• Molecular dynamics simulations of HA_Cal and HA_Ind trimers for 250 ns.
• Analysis of root-mean-square deviation (RMSD), radius of gyration (Rg), and solvent-accessible surface area (SASA).
• Dissection of cooperative and anti-cooperative motions and free energy landscape analysis.

Main Results:

• HA_Cal trimers exhibit highly dynamic monomers, with pronounced RBD dynamics.
• Mutant HA_Ind trimers show increased H-bond interactions and stabilized dynamics.
• HA_Ind displays reduced RMSD, Rg, and SASA variations, indicating enhanced stability.
• Free energy landscape analysis reveals a single stable basin for HA_Ind versus two for HA_Cal.

Conclusions:

• The mutant HA_Ind protein adopts a more stable conformation with novel functional features due to mutations.
• These findings necessitate further research into mutation-mediated changes in viral-host binding.
• The study highlights the need for developing site-specific inhibitors against emerging H1N1 variants.