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Evaluation of AlphaFold3 for the fatty acids docking to human fatty acid-binding proteins

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Nam, Ki Hyun·2024·Journal of Molecular Graphics and Modelling
DOI 10.1016/j.jmgm.2024.108872

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Abstract

Human fatty acid-binding proteins (FABPs) are involved in many aspects of lipid metabolism, such as the uptake, transport, and storage of lipophilic molecules, as well as cellular functions. Understanding how FABPs recognize fatty acids (FAs) is crucial for identifying FABP function and applications, such as in inhibitor design or biomarker development. The recently developed AlphaFold3 (AF3) demonstrates significantly higher accuracy than other prediction tools, particularly in predicting protein-ligand interactions with state-of-the-art docking tools. Studies on whether AF3 can be used to identify the FAs of FABP are lacking. To assess the accuracy of FA docking to FABPs using AF3, models of FA docked into FABP generated using AF3 were compared with experimentally determined FA-bound FABP structures. FA ligands in AF3 structures docked reliably into the FA-binding pocket of FABPs; however, the detailed binding configuration of most FA ligands docked into FABPs and the interaction between FA and FABP determined using AF3 and experimentally differed. These results will aid in understanding FA docking to FABPs and other FA-binding proteins using AF3.

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Metadata

Authors
Nam, K. H.
Affiliations
Kookmin University (KR)
Corresponding author
Nam, Ki Hyun
ORCID
Nam, Ki Hyun
Venue
Journal of Molecular Graphics and Modelling
Publisher
Elsevier BV
Published
2024-12
Volume
133
Pages
108872
ISSN
1093-3263 (ISSN-L)
DOI
10.1016/j.jmgm.2024.108872
OpenAlex
W4402930015
Cited by
21
References
3
Citations by year
2026: 9 · 2025: 12
FWCI
2.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Molecular Graphics and Modelling (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • SSRN Electronic Journal (acceptedVersion)
  • PubMed (publishedVersion)
Funders
National Research Foundation of Korea (NRF-2021R1I1A1A01050838)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
Keywords
AlphaFold3, fatty acid binding protein, protein-ligand docking, protein structure prediction, ligand binding sites, lipid metabolism, inhibitor design
MeSH terms
Binding Sites, Fatty Acids, Humans, Ligands, Protein Binding, Fatty Acid-Binding Proteins, Molecular Docking Simulation

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