Biophysical Society Thematic Meeting | Trieste 2024

Emerging Theoretical Approaches to Complement Single-Particle Cryo-EM

Poster Abstracts

3-POS Board 3 RNA-MEMBRANE INTERACTIONS: ELUCIDATING SEQUENCE SPECIFICITY VIA ENHANCED SAMPLING TECHNIQUES Salvatore Di Marco ; Jana Aupic 2 ; Giovanni Bussi 1 ; Alessandra Magistrato 2 ; 1 SISSA, Trieste, Italy 2 CNR-IOM at SISSA, Trieste, Italy Mounting evidence indicates that RNA molecules are also present on the extracellular surface of living cells. Moreover, RNA-membrane interactions are emerging as a key player in natural and synthetic biological systems, such as virions and lipid-based RNA delivery systems, respectively. While preliminary studies suggest these interactions are sequence-specific and mediated by factors such as divalent cations, RNA secondary structure and membrane phase, the molecular terms which drive RNA-membrane interactions remain poorly understood. Here, we use enhanced sampling molecular dynamics to elucidate the molecular principles governing RNA membrane interactions, considering the membrane both in their fluid and gel-like phases. In particular, we focused on characterizing the interactions between model membranes and a different set of model systems ranging from simple nucleosides to G-quadruplexes structures. G rich RNA strands have been demonstrated (Czerniak, Tomasz, and James P. Saenz. "Lipid membranes modulate the activity of RNA through sequence-dependent interactions." Proceedings of the National Academy of Sciences 119.4 (2022)) to have a strong affinity for the gel membrane. For these model systems, we estimated affinities and binding modes, validating our results on the basis of currently available experimental data. Thus, our work will highlight the molecular principles governing RNA-membrane association, broaden our understanding of RNA biological roles and could help the design and delivery of mRNA-based vaccines.

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