Inter-Subunit Dynamics Controls Tunnel Formation During the Oxygenation Process in Hemocyanin Hexamers

Area of Science:

• Biochemistry
• Structural Biology
• Computational Biology

Background:

• Hemocyanin is a copper-containing oxygen-transport protein found in arthropods.
• Horseshoe crab hemocyanin functions as a homo-hexameric protein.
• This protein exhibits distinct open and closed conformations linked to oxygenation states.

Purpose of the Study:

• To investigate the dynamic atomistic behavior of horseshoe crab hemocyanin.
• To analyze conformational changes between oxygenated and deoxygenated states.
• To understand the role of solvent cavities and tunnels in hemocyanin function.

Main Methods:

• Explicit solvent molecular dynamics simulations.
• Principal Component Analysis (PCA).
• Variational Autoencoder (VAE)-based deep learning.

Main Results:

• Detailed atomistic dynamics of oxygenated and deoxygenated hemocyanin were simulated.
• Significant variations in solvent cavities and tunnel formation were observed between states.
• PCA and deep learning successfully differentiated the dynamics of the two conformational states.
• The deoxygenated open conformation was identified to transition into a stable, closed conformation upon oxygenation.

Conclusions:

• Oxygenation induces a conformational transition in horseshoe crab hemocyanin.
• The closure of solvent cavities and tunnels is a key feature of the oxygenated state.
• Computational methods effectively capture the dynamic behavior of hemocyanin.