Protein tertiary structure and the myoglobin phase diagram

Area of Science:

• Protein Biophysics
• Theoretical Chemistry
• Structural Biology

Background:

• Understanding protein phase properties is crucial for molecular biology and drug design.
• Existing models often focus on atomic interactions, neglecting the role of overall protein structure.

Purpose of the Study:

• To develop an effective theory for investigating the phase properties of globular proteins.
• To construct the phase diagram of (apo)myoglobin using temperature and pH as thermodynamic variables.
• To elucidate the unfolding pathways and intermediate states of myoglobin.

Main Methods:

• Developed a novel theoretical approach based on a protein's tertiary structure.
• Constructed the phase diagram of (apo)myoglobin using temperature and pH.
• Analyzed protein unfolding transitions and intermediate states.

Main Results:

• Described myoglobin unfolding from native state to random coil with increasing temperature and pH.
• Confirmed two molten globule folding intermediates and predicted an abrupt transition between them.
• Identified a tricritical point where the transition line terminates, leading to fading helical structures.

Conclusions:

• The new theory effectively models protein phase properties by focusing on tertiary structure.
• Myoglobin exhibits complex phase behavior with distinct intermediate states and transitions.
• Ligand dynamics are linked to collective motions destabilizing the myoglobin F-helix.