biostudies-literatureSahrmann PGNational Institute of General Medical SciencesNIGMS NIH HHS10235-10246https://www.ebi.ac.uk/biostudies/studies/S-EPMC11604101biostudies-literatureUnknown20(22)A plethora of key biological events occur at the cellular membrane where the large spatiotemporal scales necessitate dimensionality reduction or coarse-graining approaches over conventional all-atom molecular dynamics simulation. Constructing coarse-grained descriptions of membranes systematically from statistical mechanical principles has largely remained challenging due to the necessity of capturing amphipathic self-assembling behavior in coarse-grained models. We show that bottom-up coarse-grained lipid models can possess metastable morphological behavior and that this potential metastability has ramifications for accurate development and training. We in turn develop a training algorithm which evades metastability issues by linking model training to self-assembling behavior, and demonstJournal of chemical theory and computationEnhancing the Assembly Properties of Bottom-Up Coarse-Grained Phospholipids.PMC11604101R01 GM063796R01GM063796Sahrmann PGVoth GAfalseEnhancing the Assembly Properties of Bottom-Up Coarse-Grained Phospholipids.A plethora of key biological events occur at the cellular membrane where the large spatiotemporal scales necessitate dimensionality reduction or coarse-graining approaches over conventional all-atom molecular dynamics simulation. Constructing coarse-grained descriptions of membranes systematically from statistical mechanical principles has largely remained challenging due to the necessity of capturing amphipathic self-assembling behavior in coarse-grained models. We show that bottom-up coarse-grained lipid models can possess metastable morphological behavior and that this potential metastability has ramifications for accurate development and training. We in turn develop a training algorithm which evades metastability issues by linking model training to self-assembling behavior, and demonst2024-01-01T00:00:00Z2024 Nov2026-06-05T12:51:00.658Z2026-05-17T03:08:04.553ZS-EPMC116041013953539110.1021/acs.jctc.4c00905