Attribution 4.0 International (CC BY 4.0)Zhang, ZhuoArrighi, ValeriaCampbell, LydiaLonchamp, JulienEuston, Stephen R.2023-05-022023-05-022023-04-29Zhang, Z., Arrighi, V., Campbell, L., Lonchamp, J. and Euston, S.R. (2023) ‘Molecular simulation of partially denatured β-lactoglobulin’, Food Hydrocolloids, 142, p. 108811. Available at: https://doi.org/10.1016/j.foodhyd.2023.108811.https://eresearch.qmu.ac.uk/handle/20.500.12289/13195https://doi.org/10.1016/j.foodhyd.2023.108811From Elsevier via Jisc Publications RouterHistory: accepted 2023-04-22, issued 2023-04-29Article version: AMPublication status: AcceptedFunder: Heriot-Watt University; FundRef: https://doi.org/10.13039/100009767Funder: Engineering & Physical Sciences Research Council; Grant(s): EP/J501682/1Julien Lonchamp - ORCID: 0000-0001-7954-4745 https://orcid.org/0000-0001-7954-4745The unfolding of β-lactoglobulin (β-lac) upon heating was comprehensively studied through molecular dynamics computer simulations. A β-lac molecule in the aqueous solution was firstly heated at 500 K for unfolding and then annealed at 300 K to collect stable conformations. There were five meta-stable conformations observed based on the Free Energy Landscape (FEL). The β-lac molecule was found to exhibit an open and extended conformation on heating followed by limited refolding upon cooling. The cysteine residues –SH121 and S–S66-160 in the most open conformation were located at the opposite ends of the β-lac molecule. This would favour the intermolecular –SH/S–S interchange reactions that are known to occur in β-lac as part of the inter-molecular aggregation process. Furthermore, the unfolding of the β-lac increased the hydrogen bond forming capacity between water molecules and the protein and between water molecules themselves. The interactions and the properties of the water molecules in the protein hydration shell also indicated that the hydration shell was stabilized by protein unfolding. However, it was found that the unfolding of β-lac increased diffusion of hydration water molecules, including those in the first hydration shell that interact more strongly with the protein. This may partly explain why unfolded proteins are more likely to aggregate even though there were more hydration water molecules protecting them. Such results provided more detailed information on the structure-functionality relationship of β-lac based on both the protein molecule and its hydration shell. This provides insight into how we can control the processing of proteins for desirable functional properties such as thickening and gelation, which are modified through protein-water interactions.Licence for AM version of this article starting on 2023-04-29: http://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.http://creativecommons.org/licenses/by/4.0/article2023-05-02