{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:00:50Z","timestamp":1790164850569,"version":"4.1.0"},"reference-count":44,"publisher":"AIP Publishing","issue":"12","funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CHE2003912"],"award-info":[{"award-number":["CHE2003912"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM161807"],"award-info":[{"award-number":["R35GM161807"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,28]]},"abstract":"<jats:p>Beryllium toxicity manifests as a rare lung disease, berylliosis, characterized by persistent granulomas. Studies indicate that, in the presence of Be2+, macrophage phagocytosis is markedly reduced, potentially hindering the removal of apoptotic cells. Although the exact mechanism by which Be2+ ions reduce phagocytosis is unclear, one hypothesis suggests that these small ions outcompete Ca2+ in critical ion\u2013lipid and lipid\u2013protein interactions mediating lipid recognition. To explore these interactions at the atomic level using molecular dynamics (MD), we aim to improve existing MD force fields for Be2+\u2013lipid interactions. Based on thermodynamic binding data from isothermal titration calorimetry, we have updated the CHARMM36 force field to describe interactions of Be2+ and Ca2+ with palmitoyl-oleyl phosphatidic acid (POPA), palmitoyl-oleyl phosphatidyl glycerol (POPG), and small-molecule mimics of their headgroups. Our results show that the original force field overestimated the binding affinity of Be2+ for POPA and POPG by a factor of 4\u20136. The revised parameters differentiate how ions bind to phosphate groups in monoester and diester forms. We describe the interrelationships among L-J parameters, ion coordination, and binding energies, highlighting the significant role of water in Be2+\u2013ion interactions. This work provides updated CHARMM36 force-field parameters for Be2+ and Ca2+, improving the accuracy of their interactions with potent signaling lipids, POPA and POPG, and better reflecting physiological behavior. Be2+ exhibits a stronger binding tendency, which can displace Ca2+ from its sites and hinder lipid recognition and phagocytosis.<\/jats:p>","DOI":"10.1063\/5.0345648","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:10:37Z","timestamp":1790161837000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Parameterization of the CHARMM force field for divalent cations (Ca2+\/Be2+) binding to anionic lipids with isothermal titration calorimetry"],"prefix":"10.1063","volume":"165","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6583-858X","authenticated-orcid":false,"given":"Jessica","family":"Bodosa","sequence":"first","affiliation":[{"name":"Biophysics Program, Institute for Physical Science and Technology, University of Maryland 1 , College Park, Maryland 20742,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4807-9665","authenticated-orcid":false,"given":"Sergei","family":"Sukharev","sequence":"additional","affiliation":[{"name":"Biophysics Program, Institute for Physical Science and Technology, University of Maryland 1 , College Park, Maryland 20742,","place":["USA"]},{"name":"Department of Biology, University of Maryland 2 , College Park, Maryland 20742,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8725-1870","authenticated-orcid":false,"given":"Jeffery B.","family":"Klauda","sequence":"additional","affiliation":[{"name":"Biophysics Program, Institute for Physical Science and Technology, University of Maryland 1 , College Park, Maryland 20742,","place":["USA"]},{"name":"Department of Chemical and Biomolecular Engineering, University of Maryland 3 , College Park, Maryland 20742,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"317","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"2026092307100220100_c1","doi-asserted-by":"publisher","first-page":"2763","DOI":"10.1021\/ct900364y","article-title":"Beryllium bonds, do they exist?","volume":"5","year":"2009","journal-title":"J.\u00a0Chem. 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