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Amphiphilic maleic acid-containing alternating copolymers composed of alternating maleic acid and styrene (SMA) account for a major recent methodical breakthrough in the study of membrane proteins. They were found to directly solubilize phospholipids and membrane proteins both from artificial and natural bilayers yielding discoidal SMA/lipid particles (SMALPs) [1]. SMA-encased nanolipoparticles are comprised of lipid or lipid/protein cores surrounded by a polymer belt and have, depending on the preparation routine, diameters of 10–30 nm. Within particular preparation, the size of particles is uniform, which renders them suitable for diverse experimental techniques, e.g., for cryo-electron microscopy and EPR measurements [2-3]. Although many empirical studies indicate the great potency of SMA copolymers for membrane research, the mechanisms of their action remain obscure. It is unknown what factors account for the very assembly of SMA-encased lipid particles and why they have a uniform size. We have developed a coarse-grained (CG) molecular model of SMA-polymers within the framework of the popular MARTINI CG force field. The obtained model was used to probe the behavior of SMA polymers with varying composition/charge/concentration in solution as well as their interaction with lipid membranes. The results of the simulations indicate that SMA polymers with styrene/maleic acid ratios of 2:1 and 3:1 form SMALPs by different mechanisms: either via poration or via a mechanism similar to the microvesicle release. Also, we found that the SMA polymers tend to aggregate in solution into clusters of the specific size what might account for the uniform size of the SMALPs. The work was supported by the RFBR grant No. 18-504-12045. 1. Dörr, Jonas M., et al. The styrene–maleic acid copolymer: a versatile tool in membrane research. European Biophysics Journal 45.1 (2016). doi: 10.1007/s00249-015-1093-y 2. Parmar, Mayuriben, et al. Using a SMALP platform to determine a sub-nm single particle cryo-EM membrane protein structure. BBA-Biomembranes 1860.2 (2018). doi: 10.1016/j.bbamem.2017.10.005 3. Voskoboynikova, N., et al. Characterization of an archaeal photoreceptor/transducer complex from Natronomonas pharaonis assembled within styrene–maleic acid lipid particles. RSC Advances 7.81 (2017). doi: 10.1039/C7RA10756K