Association and electrostatic steering of α-lactalbumin–lysozyme heterodimers

The salt and pH dependent association of hen egg white lysozyme with α-lactalbumin whey proteins has been studied using molecular level Monte Carlo simulations. A highly uneven charge distribution of α-lactalbumin leads to strongly ordered heterodimers that may facilitate the formation of structured, mesoscopic aggregates. This electrostatic steering gives rise to 80% alignment at 5 mM 1 : 1 salt which, due to screening, diminishes to 60% at 100 mM salt. The free energy of interaction minima, dominated by electrostatics, ranges between −9 kT at 1 mM salt to −2 kT at 100 mM (neutral pH). Calculated osmotic second virial cross coefficients indicate complexation in the pH interval 6–10. Multivalent ions are found to effectively destabilize the protein complex and, at constant ionic strength, the order is La3+ > Ca2+ > Mg2+ > Na+. Upon binding of calcium to α-lactalbumin both the interaction and orientational alignment with lysozyme are reduced due to induced changes in the whey protein charge distribution. This potentially explains the experimentally observed absence of supramolecular structuring for the calcium loaded holo α-lactalbumin. Where available, good agreement is found with experimental data.