Selective ion binding by protein probed with the statistical mechanical integral equation theory.

Area of Science:

• Biophysics
• Computational Chemistry
• Protein Science

Background:

• Selective ion binding is crucial for protein function.
• Human lysozyme and its mutants are models for studying protein-ion interactions.
• Previous studies have provided experimental data on these interactions.

Purpose of the Study:

• To theoretically investigate selective ion binding by human lysozyme and its mutants.
• To understand ion distribution within the protein cleft using computational methods.
• To compare theoretical predictions with existing experimental results.

Main Methods:

• Utilized the three-dimensional interaction site model theory (a statistical mechanical integral equation theory).
• Performed calculations for aqueous solutions of CaCl2, NaCl, and KCl.
• Analyzed four human lysozyme variants: wild type, Q86D, A92D, and Q86D/A92D.

Main Results:

• Wild type and Q86D mutant showed no significant ion distribution in the cleft.
• A92D mutant exhibited strong Na+ binding, consistent with experimental findings.
• Holo-Q86D/A92D mutant displayed higher affinity for Ca2+ than Na+, also matching experimental observations.

Conclusions:

• The theoretical model successfully predicts selective ion binding in human lysozyme mutants.
• Specific mutations, like A92D, confer distinct ion-binding properties.
• The study highlights the importance of specific residues and protein isomers in ion recognition.