Structure-based screening of protein-bioactive compatibility of upcycled jojoba oilcake proteins for nutraceutical applications.

The development of functional foods enriched with nutraceuticals offers a targeted strategy to enhance gut health and overall well-being. Protein-based matrices are increasingly explored for nutraceutical applications due to their biocompatibility, biodegradability, and ability to interact with diverse bioactive compounds. However, the rational selection of compatible protein-bioactive combinations, crucial to ensure nutraceutical efficacy, is constrained by inadequate structure-based screening. This study investigated the potential of upcycled jojoba proteins (JP) as sustainable functional matrices for nutraceutical applications using structure-based in silico screening framework. Proteins were extracted and profiled, identifying ATP synthase, Rubisco, and Clp-Protease as predominant proteins. Their 3D structures were modeled and validated for structural integrity, stability, and ligand binding. A library of 120 structurally-diverse compounds was screened using molecular docking, with 15 top candidates assessed for binding interactions, ADME properties, and complex stability. Triterpenes, flavonoids, carotenoids, and vitamins had energetically favorable interactions and stable association patterns with JP. Vitamin D3 was predicted to be a promising candidate across all protein systems, with consistent docking affinity, ADME profile, and stable MD trajectories. Fluorescence quenching analysis confirmed the interaction between JP and Vitamin D3, supporting computational predictions. These findings suggest that JP possesses inherent molecular flexibility and binding propensity relevant to nutraceutical applications, while highlighting the significance of structure-based screening as an efficient pre-formulation tool for design of next-generation protein-based delivery systems. By identifying compatible bioactives at the molecular level, this study advances structure-driven approaches for functional food formulation, reducing reliance on empirical trial-and-error approaches.