Computational insights into the lipid code of transient receptor potential vanilloid channels reveal overlap with drug binding sites
López-Martín, Mario (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Catalina-Hernández, Èric (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Peralvarez-Marin, Alex (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2025
Resum:	In this study, we characterize the plasma membrane paralipidome of the entire TRPV subfamily using microsecond coarse-grained molecular dynamics (CG-MD) simulations. We describe the lipids in the immediate protein environment, identify lipid binding regions, and map the nature of the binding sites. Key lipid interactions include cholesterol, phosphatidylinositols, phosphatidylserine, and phosphatidylethanolamine. Cholesterol shows preferential and stable binding driven by hydrophobicity to specific and conserved regions in the transmembrane domain. Phosphatidylinositols are located in polybasic patches close to the cytosolic side of the bilayer. Our findings reveal long-lasting specific interactions in previously described binding sites, but also novel lipid pockets, mapped by residue type and conservation. Our approach confirms known and uncovers new bioactive lipid binding sites, and through deeper analysis, we show lipids overlapping with drug-binding sites, which may open opportunities for lipid-based therapies and drug discovery in membrane proteins.
Ajuts:	Agencia Estatal de Investigación PID2020-120222GB-I00
Nota:	Altres ajuts: acords transformatius de la UAB
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Biomembranes ; Ion channels ; TRP channels ; Lipid-protein interactions ; Paralipidome ; Martini force field ; Bioactive lipids
Publicat a:	International journal of biological macromolecules, Vol. 330 (november 2025) , p. 148108, ISSN 1879-0003

DOI: 10.1016/j.ijbiomac.2025.148108

15 p, 21.7 MB

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