CHARMM36 All-Atom Gas Model for Lipid Nanobubble Simulation

Lipid\nnanobubbles with different gas cores may integrate the biocompatibility\nof lipids, powerful physicochemical properties of nanobubbles, and\ntherapeutic effects of gas molecules, which thus promote enormous\nbiomedical applications such as ultrasound molecular imaging, gene/drug\ndelivery, and gas therapy. In order for further more precise applications,\nthe exact molecular mechanisms for the interactions between lipid\nnanobubbles and biological systems should be studied. Molecular dynamics\n(MD) simulation provides a powerful computational tool for this purpose.\nHowever, previous state-of-the-art MD simulations of free gas nanobubble/lipid\nnanobubble employed the vacuum as their gas cores, which is not suitable\nfor studying the interactions between functional lipid nanobubbles\nand biological systems and revealing the biological roles of gas molecules.\nHence, in this work, we developed and optimized the CHARMM36 all-atom\ngas parameters for six gases including N<sub>2</sub>, O<sub>2</sub>, H<sub>2</sub>, CO, CO<sub>2</sub>, and SO<sub>2</sub>, which accurately\nreproduced the gas density at different pressures as well as the spontaneous\nformation of gas nanobubbles. Subsequent applications of these gas\nparameters for lipid nanobubble simulations also reproduced the self-assembly\nprocess of the lipid nanobubble. We further developed a Python script\nto generate all-atom lipid nanobubble simulation systems, which was\nproven to be efficient for all-atom MD simulations of lipid nanobubbles\nand to be able to capture the exact dynamics of gas molecules at the\ngas–lipid and lipid–water interfaces of the lipid nanobubble.\nIn summary, the all-atom gas models proposed in this work are suitable\nfor simulating free gas nanobubbles and lipid nanobubbles, which are\nsupposed to overcome the shortcomings of previous state-of-the-art\nMD simulations with the vacuum replacing the gas core and play key\nroles in revealing the molecular-level interactions between lipid\nnanobubbles and biological systems.