Electrostatic interactions in sperm whale myoglobin. Site specificity, roles in structural elements, and external...

Area of Science:

• Biophysics
• Protein Stability
• Electrostatics

Background:

• Sperm whale ferrimyoglobin's stability is crucial for its function.
• Understanding electrostatic contributions is key to protein stability.

Purpose of the Study:

• To evaluate the electrostatic free energy contribution to sperm whale ferrimyoglobin stability.
• To analyze the roles of interelemental and intraelemental electrostatic interactions.
• To investigate protein-solvent interface properties and charged atom accessibility.

Main Methods:

• Modified Tanford-Kirkwood model for static accessibility.
• Calculation of electrostatic free energy contributions.
• Analysis of protein surface electrostatic potentials.
• Assessment of solvent accessibility for charged atoms.

Main Results:

• Most electrostatic terms are stabilizing at pH 7, with interelemental interactions dominating.
• Short helices (C and D) are stabilized by strong intraelemental interactions compensating weak interelemental ones.
• Protein folding leads to a largely neutral interface, with two areas of nonzero potential.
• Solvent accessibility of charged atoms is primarily dictated by nonpolar atoms, suggesting a dielectric shielding role.

Conclusions:

• Electrostatic interactions play a vital stabilizing role in ferrimyoglobin.
• Structural elements dynamically adjust electrostatic interactions to accommodate pH variations.
• Nonpolar atoms are critical for shielding charged atoms and influencing protein stability beyond hydrophobic effects.