2026-04-14T02:06:30Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4862042025-08-31T18:30:03Zcom_2072_98col_2072_378192

Membrane disruption potential of endogenous opioid neuropeptide Dynorphin A and related clinical variants Catalina-Hernández, Èric López-Martín, Mario Aguilella-Arzo, Marcel Peralvarez-Marin, Alex Dynorphins Membrane transport Neuropeptides Peptide-bilayer interactions Membrane disturbing potential Molecular dynamics simulations Altres ajuts: acords transformatius de la UAB Dynorphins are natural neuropeptides that act like opioids but can also cause harmful effects like neurological issues and cell death. Dynorphin A (DynA WT) and its variants (L5S, R6W, and R9C) may disrupt lipid bilayers, leading to pathophysiological effects. Using steered and conventional molecular dynamics simulations, we evaluated how DynA and its variants interact with and penetrate model lipid bilayers. We defined three lipid compositions: neutral, cholesterol-rich and negatively charged, representing different sections of a cell membrane to characterize specific lipid-protein interactions. The R6W peptide cannot find a stable state in any membrane, always returning to the water-bilayer interface. DynA L5S uniquely disturbs neutral lipid bilayers by forming proteolipid pores at the hydrophobic core. DynA WT and L5S are capable to form more stable proteolipid pores in neutral bilayers with cholesterol. L5S and R9C disrupt negatively charged bilayers with cholesterol, again, being able to form stable toroidal pores. The computational strategy presented here allows to study how single amino acid changes in DynA peptides affect their ability to disturb different bilayer compositions. 2025 Article https://ddd.uab.cat/record/313553 urn:10.1016/j.ijbiomac.2025.144567 urn:oai:ddd.uab.cat:313553 urn:scopus_id:105006763229 urn:articleid:18790003v316p144567 urn:pmid:40412686 urn:oai:egreta.uab.cat:publications/34e1df51-dcf8-4b2f-ad03-8ce0572ea8b0 http://hdl.handle.net/2072/486204 eng International journal of biological macromolecules ; Vol. 316 (june 2025), p. 144567 open access 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. https://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf