Using THz Spectroscopy, Evolutionary Network Analysis Methods, and MD Simulation to Map the Evolution of Allosteric...

Area of Science:

• Protein evolution
• Biophysics
• Molecular mechanisms

Background:

• Protein function is linked to energy landscape navigation, involving ensembles of conformations rather than single structures.
• Evolution modifies protein function by altering these landscapes through selective pressures on conformational sampling.

Purpose of the Study:

• Elucidate the evolutionary pathway shaping mammalian c-type lysozyme subfamily functions.
• Identify molecular mechanisms and intermolecular interactions governing conformational states and novel functions.

Main Methods:

• Experimental and computational approaches were employed.
• Contrasted three representative proteins within the subfamily.
• Mapped intermolecular interactions influencing conformational sampling and energy landscapes.

Main Results:

• Identified molecular mechanisms for enhanced antimicrobial properties and divergent functions.
• Linked localized fluctuations in the A-B helix loop to conformational ensemble shifts.
• Demonstrated impact on interdomain coupling and substrate binding affinity.

Conclusions:

• Revealed molecular insights into immune response, infection, and lactation nutritional properties.
• Provided a deeper understanding of how evolving energy landscapes define current protein function.
• Highlighted the role of specific structural elements in mediating functional divergence.