Liposomes are essential systems in biophysics and biotechnology, with cholesterol acting as a central regulator of bilayer structure and dynamics. Coarse-grained molecular dynamics (CG-MD) with the MARTINI force field has been widely used to investigate lipid membranes, yet large-scale vesicle simulations remain computationally demanding. In this study, we constructed and simulated DOPC/cholesterol vesicles of ∼50 nm diameter across different cholesterol concentrations using both wet MARTINI and dry MARTINI. For the dry MARTINI systems, vesicles were generated with the TS2CG method. This setup allowed us to directly evaluate and compare the performance of both approaches for cholesterol-containing vesicles of the same size and composition. We analyzed key structural and dynamic properties, including bilayer thickness, solvent-accessible surface area per lipid, leaflet redistribution, lipid interdigitation, and transbilayer exchange (flip-flop). Our analysis focused on whether both models exhibited comparable trends and whether dry MARTINI could reproduce essential cholesterol-dependent behaviors while reducing computational cost. This approach enabled efficient exploration of vesicle-scale organization and cholesterol-dependent dynamics at mesoscopic length scales. Our results provided a direct comparison between dry and wet MARTINI models for vesicle simulations and assessed their ability to capture cholesterol-driven structural and dynamic features. These findings highlighted the potential of dry MARTINI to extend the feasible size and time scales of liposome modeling, while complementing wet MARTINI in studies relevant to membrane biophysics and nanomedicine.
Khodadadi et al. (Sun,) studied this question.