Probing the binding stability of organic UV filters to human SLC transporters using AlphaFold and molecular dynamics simulations

Abstract

Abstract The ubiquitous presence of organic ultraviolet filters (UVFs) in environmental and human, driven by their heavy usage in personal care formulations, has raised significant concern. Despite this, the transmembrane transport mechanisms of UVFs—key to understanding cutaneous absorption and organ-specific toxicity—remain poorly defined. To bridge this gap, this study coupled molecular docking with molecular dynamics (MD) simulations to systematically screen the interactions between various UVFs and solute carrier (SLC) transporters. Through the analysis of 23,970 complex pairs, we identified distinct binding behaviors. Specifically, Tris-biphenyl triazine (TBPT) and Diethylhexyl butamido triazone (DBT) formed highly stable complexes with SLC22A31 and SLC29A4, respectively, exhibiting strong binding affinities (− 10.8 and − 9.8 kcal/mol). Over 200 ns simulations, these complexes maintained ligand Root Mean Square Deviation (RMSD) values below 5 Å. Crucially, per-residue interaction profiling revealed that this persistent stability is governed by high-occupancy (> 80%) hydrophobic anchors, which form rigid “hydrophobic traps” around the lipophilic UVFs. Conversely, the Pentyl 4-(dimethylamino) benzoate (APABA) and TMEM163 complex demonstrated weak interaction (− 3.9 kcal/mol) with significant structural instability, indicated by progressive ligand escape and RMSD values exceeding 15 Å. These findings elucidate how specific UVF-SLC interactions, driven by local hydrophobic complementarity, may facilitate localized toxicological effects, offering a novel computational framework for assessing the transmembrane health risks associated with organic UVFs exposure.