Lactoferrin (Lf) is increasingly of interest in the food industry due to its significant health benefits. In order to preserve its functional properties under various processing regimes, whey protein isolate (WPI) has been proposed as an encapsulant. Recent studies have elucidated the stability of Lf and WPI, and the complex formed between these at food processing temperatures. However, the effect of simulated gastric conditions has not been evaluated. Accordingly, the objective of this study has been to investigate the behaviour of apo-Lf, the least stable form of Lf under gastric pH conditions using molecular dynamics simulations. This was extended to interactions with α-lactalbumin (α-La) and β-lactoglobulin (β-Lg), two of the primary constituents of WPI. The data show that at the acidic pH, apo-Lf has weaker interactions with both β-Lg and α-La, compared to those at neutral pH. Nevertheless, free energy calculations for protein-protein dissociation using umbrella sampling indicate that intermittent contacts are maintained between apo-Lf and β-Lg units, resulting in a broad energy minimum point at intermediate distance, possible flocculation composed of protein particles, and eventual gel formation. This property may be exploited to entrap further bioactive components within the protein matrix for novel engineered food materials. Per-residue evaluations at a range of distances between apo-Lf and β-Lg units were also calculated. The results indicated a reduction in the movements of most residues with decreasing separation, highlighting those residues whose motions are most sensitive to inter-protein distance and may play important roles in sustaining long-range interactions. Overall, this work demonstrates the advantages of in silico methods as novel tools in understanding the structural changes of apo-Lf and the interaction with α-La and β-Lg that may benefit future development of nutraceuticals.