• Non-covalent assembly of folic...

*Result*: Non-covalent assembly of folic acid with lactoferrin: multi-spectroscopy, docking, and dynamics elucidate binding and functional implications.

Title:
Non-covalent assembly of folic acid with lactoferrin: multi-spectroscopy, docking, and dynamics elucidate binding and functional implications.
Authors:
Xu Y; College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, China., Tang R; College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, China., Zhang Z; College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, China., Liu J; College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, China., Pu Y; College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, China., Zhao R; College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, China; Food Laboratory of Zhongyuan, Henan University of Technology, Zhengzhou, Henan 450001, China., Liu Z; College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, China; Food Laboratory of Zhongyuan, Henan University of Technology, Zhengzhou, Henan 450001, China. Electronic address: liuzehua@haut.edu.cn., Jiang H; College of Food Science and Technology, Henan University of Technology, Zhengzhou, Henan 450001, China; Food Laboratory of Zhongyuan, Henan University of Technology, Zhengzhou, Henan 450001, China. Electronic address: hongxin.jiang@haut.edu.cn.
Source:
Food research international (Ottawa, Ont.) [Food Res Int] 2026 Jan; Vol. 223 (Pt 1), pp. 117824. Date of Electronic Publication: 2025 Nov 11.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science Country of Publication: Canada NLM ID: 9210143 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7145 (Electronic) Linking ISSN: 09639969 NLM ISO Abbreviation: Food Res Int Subsets: MEDLINE
Imprint Name(s):
Original Publication: Ottawa, Ontario, Canada : Published on behalf of the Canadian Institute of Food Science and Technology by Elsevier Applied Science, c1992-
MeSH Terms:
Lactoferrin*/chemistry , Lactoferrin*/metabolism , Folic Acid*/chemistry , Folic Acid*/metabolism , Molecular Docking Simulation*, Hydrogen Bonding ; Hydrogen-Ion Concentration ; Molecular Dynamics Simulation ; Hydrophobic and Hydrophilic Interactions ; Protein Binding ; Spectrometry, Fluorescence ; Spectrophotometry, Ultraviolet ; Humans
Contributed Indexing:
Keywords: Folic acid; Functional property; Lactoferrin; Molecular dynamics simulation; Multispectral analysis; Non-covalent binding; pH stability
Substance Nomenclature:
EC 3.4.21.- (Lactoferrin)
935E97BOY8 (Folic Acid)
Entry Date(s):
Date Created: 20251206 Date Completed: 20251206 Latest Revision: 20251206
Update Code:
20260130
DOI:
10.1016/j.foodres.2025.117824
PMID:
41352785
Database:
MEDLINE

*Further Information*

*Folic acid (FA) is important for human health, but it is sensitive to pH and can degrade during gastrointestinal digestion. Therefore, direct FA supplementation is limited. In this study, lactoferrin (LF) was used to prepare an LF-FA complex through a non-covalent interaction. LF significantly improves the pH stability (90.36 % at pH 2.1) and retention rate (59.19 %) of FA after in vitro digestion, compared with those of free FA (70.56 and 34.53 %). Furthermore, fluorescence and ultraviolet (UV) spectroscopy revealed that FA binding alters the secondary structure of LF, increasing the α-helix context and decreasing β-sheet structures. This interaction leads to complex formation through hydrogen bonding and hydrophobic interactions. Isothermal titration curves revealed that the LF-FA complex undergoes a spontaneous static quenching process, suggesting that the interaction is primarily driven by hydrogen bonds and van der Waals forces (ΔH = -97.37 kJ·mol<sup>-1</sup>, ΔS = -224.42 J·mol<sup>-1</sup>). Furthermore, molecular docking and molecular dynamics simulations indicated that FA stably binds to key residues of LF, such as Asp60 and Tyr192, through hydrogen bonds and hydrophobic interactions. This enhances the structural rigidity of the complex and stabilizes the free energy landscape. These results not only improve the shortcomings of directly adding FA, but also provide references for the development of other similar products and expand the application scenarios of FA.
(Copyright © 2025 Elsevier Ltd. All rights reserved.)*

*Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.*