Coarse-grained molecular dynamics investigation on the interaction between κ- and β-casein aggregates and curcumin

Abstract

Caseins, the predominant proteins in milk, play a crucial role in the formation of micellar complexes due to their amphiphilic nature, which facilitates the formation of micellar complexes, with κ-casein stabilizing micelle formation. Understanding the self-assembly of casein molecules is essential for exploring their potential applications, such as nanoencapsulation of bioactive compounds. This study delves into the structural properties and self-assembly mechanisms of κ-casein and β-casein using computational models and simulations. Through coarse-grained (CG) modeling, the study investigates the stable structure of an aggregate composed of -casein and β-casein after 1 μs of CG simulation, highlighting a loose arrangement with water molecules in the cavity. Simulations of the encapsulation process for the bioactive compound show that the curcumin tends to adhere to the surface of the casein aggregate and cannot spontaneously be encapsulated by casein. Additionally, Steered Molecular Dynamics (SMD) simulations shed light on the interaction between the aggregate and curcumin, illustrating the challenges faced by insoluble compounds in entering casein micelles due to the tightly packed arrangement of κ-casein. Based on the simulation results, the curcumin can’t penetrate the casein aggregate spontaneously. External forces, such as homogenization and ultrasonication, are required to overcome the energy barrier and facilitate the complexation of curcumin with caseins. These findings provide theoretical guidance for using caseins as encapsulation agents for hydrophobic functional compounds.