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Updated: May 10, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Ligand binding promiscuity of human liver fatty acid binding protein: structural and dynamic insights from an
Filippo Favretto1, Michael Assfalg, Mariana Gallo
1NMR laboratory, Department of Biotechnology, University of Verona, Strada le Grazie 15, 37134 Verona (Italy).
Abstract:
Human liver fatty acid binding protein (hL-FABP) has been reported to act as an intracellular shuttle of lipid molecules, thus playing a central role in systemic metabolic homeostasis. The involvement of hL-FABP in the transport of bile salts has been postulated but scarcely investigated. Here we describe a thorough NMR investigation of glycocholate (GCA) binding to hL-FABP. The protein molecule bound a single molecule of GCA, in contrast to the 1:2 stoichiometry observed with fatty acids. GCA was found to occupy the large internal cavity of hL-FABP, without requiring major conformational rearrangement of the protein backbone; rather, this led to increased stability, similar to that estimated for the hL-FABP:oleate complex. Fast-timescale dynamics appeared not to be significantly perturbed in the presence of ligands. Slow motions (unlike for other proteins of the family) were retained or enhanced upon binding, consistent with a requirement for structural plasticity for promiscuous recognition.
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