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Here, we combine atomistic molecular dynamics (MD) simulations with double electron\u2013electron resonance (DEER), using hydrostatic pressure as a reversible thermodynamic perturbation to shift conformational equilibria and stabilize low\u2010population states. MD simulations reveal localized intrinsic flexibility within\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010strands\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1\u2013\n                    <jats:italic>\u03b2<\/jats:italic>\n                    5 and\n                    <jats:italic>\u03b2<\/jats:italic>\n                    19, as well as in cytosolic loops connecting\n                    <jats:italic>\u03b2<\/jats:italic>\n                    6\u2013\n                    <jats:italic>\u03b2<\/jats:italic>\n                    7 and\n                    <jats:italic>\u03b2<\/jats:italic>\n                    8\u2013\n                    <jats:italic>\u03b2<\/jats:italic>\n                    9. High\u2010pressure DEER measurements in lipid nanodiscs corroborate these predictions, identifying reversible, pressure\u2010dependent distance changes within the pore lumen consistent with asymmetric deformation of the\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010barrel. DEER\u2010informed analysis of unbiased MD trajectories reveals an elliptical\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010barrel conformation aligned parallel to the N\u2010terminal helix that corresponds to the pressure\u2010stabilized experimental state. ATP permeation simulations identify a free\u2010energy barrier to metabolite translocation in this elliptical geometry, whereas diffusion through the circular open state is energetically favorable. These findings indicate that the elliptical conformation represents a transient gating\u2010competent state rather than a fully closed channel. Together, our results support a gating mechanism driven by reversible\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010barrel deformation and establish pressure\u2010perturbed DEER integrated with MD as a general strategy for capturing transient, functionally relevant conformations of membrane channels.\n                  <\/jats:p>","DOI":"10.1002\/pro.70677","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T12:50:11Z","timestamp":1781873411000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elliptical\n                    <scp>\n                      <i>\u03b2<\/i>\n                    <\/scp>\n                    \u2010barrel deformation underlies gating in\n                    <scp>VDAC1<\/scp>"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6068-238X","authenticated-orcid":false,"given":"L.","family":"Bergdoll","sequence":"first","affiliation":[{"name":"Laboratoire d'Ing\u00e9nierie des Syst\u00e8mes Macromol\u00e9culaires CNRS, UMR 7255\u2014Aix Marseille Universit\u00e9  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0550-4852","authenticated-orcid":false,"given":"M.","family":"Elgeti","sequence":"additional","affiliation":[{"name":"Institute for Drug Discovery and Institute for Medical Physics and Biophysics, Leipzig University, Faculty of Medicine  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Belyaeva","sequence":"additional","affiliation":[{"name":"Institute for Drug Discovery and Institute for Medical Physics and Biophysics, Leipzig University, Faculty of Medicine  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8627-0455","authenticated-orcid":false,"given":"A.","family":"Zlobin","sequence":"additional","affiliation":[{"name":"Institute for Drug Discovery, Leipzig University, Faculty of Medicine  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P.","family":"Duneau","sequence":"additional","affiliation":[{"name":"Laboratoire d'Ing\u00e9nierie des Syst\u00e8mes Macromol\u00e9culaires CNRS, UMR 7255\u2014Aix Marseille Universit\u00e9  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Hubbell","sequence":"additional","affiliation":[{"name":"Stein Eye Institute, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0004-7426","authenticated-orcid":false,"given":"J.","family":"Abramson","sequence":"additional","affiliation":[{"name":"Department of Physiology, David Geffen School of Medicine University of California, Los Angeles  Los Angeles California 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