Multi-proton dynamics near membrane-water interface

Abstract Protons are crucial for biological energy transduction between membrane proteins. While experiments suggest rapid proton motion over large distances at the membrane-water interface, computational studies employing a single excess proton found the proton immobilized near the lipid headgroup....

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Main Authors: Subhasish Mallick, Noam Agmon
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58167-w
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author Subhasish Mallick
Noam Agmon
author_facet Subhasish Mallick
Noam Agmon
author_sort Subhasish Mallick
collection DOAJ
description Abstract Protons are crucial for biological energy transduction between membrane proteins. While experiments suggest rapid proton motion over large distances at the membrane-water interface, computational studies employing a single excess proton found the proton immobilized near the lipid headgroup. To address this discrepancy, we conduct DFTB3 simulations by incrementally adding protons up to three. We show that a single proton moves rapidly toward the nearest headgroup, where it is either repelled by a choline group or binds covalently to phosphatic oxygen. With multiple protons, while some are trapped by the lipid headgroups, the remaining proton diffuses laterally faster than in bulk water. Driven by excess energy, this proton initially jumps to the center of the water slab before relaxing into the third- and second-hydration shells. Lateral diffusion rates increase as the proton stabilizes in the second hydration shell. These results provide insights into proton dynamics near membranes and explain experimental observations.
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spelling doaj-art-e5ddc9ab775542cb98c26eb193c4e9822025-08-20T02:25:41ZengNature PortfolioNature Communications2041-17232025-04-0116111010.1038/s41467-025-58167-wMulti-proton dynamics near membrane-water interfaceSubhasish Mallick0Noam Agmon1The Fritz Haber Research Center, Institute of Chemistry, The Hebrew University of JerusalemThe Fritz Haber Research Center, Institute of Chemistry, The Hebrew University of JerusalemAbstract Protons are crucial for biological energy transduction between membrane proteins. While experiments suggest rapid proton motion over large distances at the membrane-water interface, computational studies employing a single excess proton found the proton immobilized near the lipid headgroup. To address this discrepancy, we conduct DFTB3 simulations by incrementally adding protons up to three. We show that a single proton moves rapidly toward the nearest headgroup, where it is either repelled by a choline group or binds covalently to phosphatic oxygen. With multiple protons, while some are trapped by the lipid headgroups, the remaining proton diffuses laterally faster than in bulk water. Driven by excess energy, this proton initially jumps to the center of the water slab before relaxing into the third- and second-hydration shells. Lateral diffusion rates increase as the proton stabilizes in the second hydration shell. These results provide insights into proton dynamics near membranes and explain experimental observations.https://doi.org/10.1038/s41467-025-58167-w
spellingShingle Subhasish Mallick
Noam Agmon
Multi-proton dynamics near membrane-water interface
Nature Communications
title Multi-proton dynamics near membrane-water interface
title_full Multi-proton dynamics near membrane-water interface
title_fullStr Multi-proton dynamics near membrane-water interface
title_full_unstemmed Multi-proton dynamics near membrane-water interface
title_short Multi-proton dynamics near membrane-water interface
title_sort multi proton dynamics near membrane water interface
url https://doi.org/10.1038/s41467-025-58167-w
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AT noamagmon multiprotondynamicsnearmembranewaterinterface