Electrostatic free energy of lysozyme

Area of Science:

• Biochemistry
• Physical Chemistry
• Protein Chemistry

Background:

• Understanding protein stability is crucial for molecular biology and drug development.
• Electrostatic interactions significantly influence protein structure and function.
• Lysozyme's stability is affected by modifications such as acetylation.

Purpose of the Study:

• To compute the electrostatic free energies of native and acetylated lysozymes.
• To assess the stability differences between native and acetylated lysozyme using computational methods.
• To investigate the contribution of individual charges to protein stabilization and apparent pK values.

Main Methods:

• Utilized the fixed charge model (Tanford and Kirkwood) for electrostatic free energy calculations.
• Transformed charges into a sphere of fixed radius, maintaining charge depths proportional to accessibility.
• Optimized a conversion factor (1.62 Å) for best fit between computed and experimental titration curves.

Main Results:

• Calculated electrostatic free energies indicated that acetylated lysozyme is less stable than native lysozyme around neutral pH.
• The computational model successfully reproduced experimental titration data when using a conversion factor of 1.62 Å.
• Determined the contribution of each charge to protein stabilization and computed apparent pK values for ionizable groups.

Conclusions:

• The fixed charge model provides a reliable method for calculating electrostatic free energies and assessing protein stability.
• Acetylation of lysozyme leads to decreased protein stability, particularly at neutral pH.
• The study highlights the importance of electrostatic interactions in determining protein stability and the behavior of ionizable groups.