{"about":{"site":"https://codewithpapers.app","non_affiliation":"Code with Papers and Syntology are not affiliated with, endorsed by, or sponsored by Papers with Code, Meta, or the pwc-archive mirror.","licence":"CC BY-SA 4.0","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","attribution":"https://codewithpapers.app/attribution","modified":"archive material modified by Syntology; see the attribution page"},"url":"/paper/characterizing-rna-oligomers-using-stochastic","title":"Characterizing RNA oligomers using Stochastic Titration Constant-pH Metadynamics simulations","arxiv_id":"2410.16064","date":"2024-10-21","proceeding":null,"authors":["Tomas F. D. Silva","Giovanni Bussi"],"abstract":"RNA molecules exhibit various biological functions intrinsically dependent on their diverse ecosystem of highly flexible structures. This flexibility arises from complex hydrogen-bonding networks defined by canonical and non-canonical base pairs that require protonation events to stabilize or perturb these interactions. Constant pH molecular dynamics (CpHMD) methods provide a reliable framework to explore the conformational and protonation space of dynamic structures and for robust calculations of pH-dependent properties, such as the pK$_\\mathrm{a}$ of titrable sites. Despite growing biological evidence concerning pH regulation of certain motifs and in biotechnological applications, pH-sensitive in silico methods have rarely been applied to nucleic acids. In this work, we extended the stochastic titration CpHMD method to include RNA parameters from the standard $\\chi$OL3 AMBER force field and highlighted its capability to depict titration events of nucleotides in single-stranded RNAs. We validated the method using trimers and pentamers with a single central titrable site while integrating a well-tempered metadynamics approach into the st-CpHMD methodology (CpH-MetaD) using PLUMED. This approach enhanced the convergence of the conformational landscape and enabled more efficient sampling of protonation-conformation coupling. Our pK$_\\mathrm{a}$ estimates agree with experimental data, validating the method's ability to reproduce electrostatic changes around a titrable nucleobase in single-stranded RNA. These findings provided molecular insight into intramolecular phenomena, such as nucleobase stacking and phosphate interactions, that dictate the experimentally observed pK$_\\mathrm{a}$ shifts between different strands. Overall, this work validates both the st-CpHMD and the metadynamics integration as reliable tools for studying biologically relevant RNA systems.","url_abs":"https://arxiv.org/abs/2410.16064v2","url_pdf":"https://arxiv.org/pdf/2410.16064v2.pdf","source":{"archive":"pwc-archive (Hugging Face), CC BY-SA 4.0","snapshot":"2025-07-28","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","row_kind":"abstracts"},"code_links":[{"paper_slug":"characterizing-rna-oligomers-using-stochastic","repo_url":"https://github.com/tomfersil/cph-metad","is_official":1,"mentioned_in_paper":1,"mentioned_in_github":1,"framework":"none","reach":null}],"tasks":[],"methods":[{"method_slug":"base","method_name":"BASE"}],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"syntology_url":null,"atlas_url":null,"mcp":null,"developers":"https://syntology.ai/developers"},"arxiv_metadata":null,"syntology_extracted_results":null}