Effect of Oxidation on Cx26 Gap Junctions: A Molecular Dynamics Study.

Area of Science:

• Cellular biology
• Biophysics
• Computational chemistry

Background:

• Gap junctions (GJs) facilitate intercellular communication via connexin (Cx) proteins, crucial for physiological processes.
• Cold atmospheric plasma (CAP) and other oxidative stress therapies show anticancer potential, but GJ role in RONS propagation is unclear.
• The impact of reactive oxygen and nitrogen species (RONS) on GJ functionality and oxidative post-translational modifications remains under-explored.

Purpose of the Study:

• To investigate the atomic-level effects of oxidative stress on Cx26 gap junctions (Cx26-GJs).
• To compare oxidized and non-oxidized Cx26-GJ structures using molecular dynamics simulations.
• To determine how oxidation influences GJ structure, conformation, stability, and permeability.

Main Methods:

• Atomistic molecular dynamics (MD) simulations were employed.
• Simulated oxidation of amino acids within a Cx26-GJ structure.
• Compared oxidized structures against a non-oxidized Cx26-GJ control.

Main Results:

• Oxidation significantly alters the structure and intermolecular interactions of Cx26-GJs.
• Reduced binding free energy between hemichannels was observed in oxidized GJs.
• A decrease in the central pore diameter of Cx26-GJs was detected upon oxidation.

Conclusions:

• Oxidative stress impacts Cx26-GJ structure and stability.
• Altered GJ properties due to oxidation may affect intercellular communication and molecule transport.
• Findings provide insights into oxidative stress-based cancer therapies and GJ function.