Strong electrostatic attraction drives milk heteroprotein complex coacervation

Summary, in English

Coacervates of oppositely charged milk proteins are used in functional food development, mainly to encapsulate bioactives. To uncover the driving forces behind coacervates formation, we study the association of lactoferrin and β−lactoglobulin at amino-acid level detail, using molecular simulations. Our findings show that inter-protein electrostatic interactions dominate and are, surprisingly, equally divided between an isotropic part, due to monopole-monopole attraction of the oppositely charged proteins, and an anisotropic part due to uneven surface charge distributions. In good agreement with recent experimental association constants, the calculated protein-protein interaction free energy is strongly dependent on pH and salt concentration. In addition to thermodynamics, we also investigate amino acid contacts in microstates of trimeric and pentameric protein complexes, and identify interaction hot-spots that drive heteroprotein complex coacervation process.

• Author: Isabel Vinterbladh; Rima Hachfi Soussi; Jan Forsman; Said Bouhallab; Mikael Lund
• Department/s: Computational Chemistry; eSSENCE: The e-Science Collaboration
• Publishing year: 2025-01
• Language: English
• Publication/Series: International Journal of Biological Macromolecules
• Volume: 286
• Links: http://dx.doi.org/10.1016/j.ijbiomac.2024.137790
• Document type: Journal article
• Publisher: Elsevier
• Topic: Physical Chemistry (including Surface- and Colloid Chemistry); Theoretical Chemistry (including Computational Chemistry)
• Keywords: Coacervates; Heteroprotein complex coacervation; Lactoferrin; Metropolis-Hastings Monte Carlo; Milk proteins; Parallel tempering; β-lactoglobulin
• Status: Published
• ISBN/ISSN/Other: ISSN: 0141-8130