Numerical studies of strong protein interactions

Protein–protein interactions are fundamental to biological functions as well as the design of new functional food products and biomedicines. However, they can be challenging to computationally quantify due to strong forces and sensitivity to pronounced solution conditions. This thesis combines computational methods with Monte Carlo simulations to investigate strong protein interactions in diverse systems.Paper I uses Monte Carlo simulations to study heteroprotein complex coacervation between the milk proteins lactoferrin and β−lactoglobulin. Both implicit and explicit salt simulations are performed. The explicit ones with the help of parallel tempering, where agreement with experimental observations is obtained. A residue–residue contact analysis at the free energy minimum is performed, where key interaction sites on the proteins are identified.Paper II investigates the thermodynamic consequences of structural variability in haemoglobins from six mammalian species. One- and two-body Monte Carlo simulations quantify electrostatic properties and second osmotic virial coefficients, revealing differences inanisotropy and interaction strength.Paper III introduces a general computational framework for evaluating two-body partition functions and quantifying respective thermodynamic properties. By discretising relative orientations on a quasi-regular angular grid, the method efficiently captures anisotropic interactions, agrees with Monte Carlo results for a benchmarking system, and highlights limitations of a current coarse-grained force field when off-centre charge distributions are important.Conclusively, this work contributes to a better understanding of protein–protein interactions, provides tools for accurately computing thermodynamic properties of anisotropic biomolecules, and demonstrates applications ranging from food proteins to haemoglobins.