Polymeric Properties of Higher-Order G-Quadruplex Telomeric Structures: Effects of Chemically Inert Crowders
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arXiv
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| Format: | Preprint |
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2024
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| author | Mostarac, Deniz Trapella, Mattia Bertini, Luca Comez, Lucia Paciaroni, Alessandro De Michele, Cristiano |
| author_facet | Mostarac, Deniz Trapella, Mattia Bertini, Luca Comez, Lucia Paciaroni, Alessandro De Michele, Cristiano |
| contents | G-quadruplexes are non-canonical DNA structures rather ubiquitous in human genome, which are thought to play a crucial role in the development of 85-90 % of cancers. Here, we present a novel coarse-grained approach in modeling G-quadruplexes which accounts for their structural flexibility. We apply it to study the polymeric properties of G-quadruplex multimers, with and without crowder particles, to mimic in-vivo conditions. We find that, contrary to some suggestions found in the literature, long G-quadruplex multimers are rather flexible polymeric macromolecules, with a local persistence length comparable to monomer size, exhibiting chain stiffness variation profile consistent with a real polymer in good solvent. Moreover, in a crowded environment (up to 10% volume fraction), we report that G-quadruplex multimers exhibit an increased propensity for coiling, with a corresponding decrease in the measured chain stiffness. Accurately accounting for the polymeric properties of G4 multimers is crucial for understanding their interactions with anticancer G4-targeting drugs, thereby significantly enhancing the design and effectiveness of these drugs. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2408_07415 |
| institution | arXiv |
| publishDate | 2024 |
| record_format | arxiv |
| spellingShingle | Polymeric Properties of Higher-Order G-Quadruplex Telomeric Structures: Effects of Chemically Inert Crowders Mostarac, Deniz Trapella, Mattia Bertini, Luca Comez, Lucia Paciaroni, Alessandro De Michele, Cristiano Computational Physics Soft Condensed Matter G-quadruplexes are non-canonical DNA structures rather ubiquitous in human genome, which are thought to play a crucial role in the development of 85-90 % of cancers. Here, we present a novel coarse-grained approach in modeling G-quadruplexes which accounts for their structural flexibility. We apply it to study the polymeric properties of G-quadruplex multimers, with and without crowder particles, to mimic in-vivo conditions. We find that, contrary to some suggestions found in the literature, long G-quadruplex multimers are rather flexible polymeric macromolecules, with a local persistence length comparable to monomer size, exhibiting chain stiffness variation profile consistent with a real polymer in good solvent. Moreover, in a crowded environment (up to 10% volume fraction), we report that G-quadruplex multimers exhibit an increased propensity for coiling, with a corresponding decrease in the measured chain stiffness. Accurately accounting for the polymeric properties of G4 multimers is crucial for understanding their interactions with anticancer G4-targeting drugs, thereby significantly enhancing the design and effectiveness of these drugs. |
| title | Polymeric Properties of Higher-Order G-Quadruplex Telomeric Structures: Effects of Chemically Inert Crowders |
| topic | Computational Physics Soft Condensed Matter |
| url | https://arxiv.org/abs/2408.07415 |