Fig. . Representing the fragment-based approach to construct several ionizable lipid models. A) The funnel illustrates the fragment-based approach and the step-by-step process for constructing an ionizable lipid. It begins with headgroup fragments and their corresponding names in the larger section of the funnel, followed by additional linker fragments that can be incorporated. Finally, the tails are attached to complete the lipid structure. B) Solvent Accessible Surface Area (SASA) for atomistic vs coarse grained fragments. C) COSMO-RS vs CG calculated partitioning free energies for the coarse grained fragments. D) The chemical structure of the ALC-0315 ionizable lipid is depicted, with the head, linker, and tails regions highlighted to correspond with the colors shown in the funnel above. Additionally, examples of other key components of a LNP are presented, including sterol, helper lipid, PEGylated lipid, and RNA cargo.