--- _id: '804' abstract: - lang: eng text: Polysaccharides (carbohydrates) are key regulators of a large number of cell biological processes. However, precise biochemical or genetic manipulation of these often complex structures is laborious and hampers experimental structure–function studies. Molecular Dynamics (MD) simulations provide a valuable alternative tool to generate and test hypotheses on saccharide function. Yet, currently used MD force fields often overestimate the aggregation propensity of polysaccharides, affecting the usability of those simulations. Here we tested MARTINI, a popular coarse-grained (CG) force field for biological macromolecules, for its ability to accurately represent molecular forces between saccharides. To this end, we calculated a thermodynamic solution property, the second virial coefficient of the osmotic pressure (B22). Comparison with light scattering experiments revealed a nonphysical aggregation of a prototypical polysaccharide in MARTINI, pointing at an imbalance of the nonbonded solute–solute, solute–water, and water–water interactions. This finding also applies to smaller oligosaccharides which were all found to aggregate in simulations even at moderate concentrations, well below their solubility limit. Finally, we explored the influence of the Lennard-Jones (LJ) interaction between saccharide molecules and propose a simple scaling of the LJ interaction strength that makes MARTINI more reliable for the simulation of saccharides. acknowledged_ssus: - _id: ScienComp acknowledgement: P.S.S. was supported by research fellowship 2811/1-1 from the German Research Foundation (DFG), and M.S. was supported by EMBO Long Term Fellowship ALTF 187-2013 and Grant GC65-32 from the Interdisciplinary Centre for Mathematical and Computational Modelling (ICM), University of Warsaw, Poland. The authors thank Antje Potthast, Marek Cieplak, Tomasz Włodarski, and Damien Thompson for fruitful discussions and the IST Austria Scientific Computing Facility for support. article_processing_charge: No author: - first_name: Philipp S full_name: Schmalhorst, Philipp S id: 309D50DA-F248-11E8-B48F-1D18A9856A87 last_name: Schmalhorst orcid: 0000-0002-5795-0133 - first_name: Felix full_name: Deluweit, Felix last_name: Deluweit - first_name: Roger full_name: Scherrers, Roger last_name: Scherrers - first_name: Carl-Philipp J full_name: Heisenberg, Carl-Philipp J id: 39427864-F248-11E8-B48F-1D18A9856A87 last_name: Heisenberg orcid: 0000-0002-0912-4566 - first_name: Mateusz K full_name: Sikora, Mateusz K id: 2F74BCDE-F248-11E8-B48F-1D18A9856A87 last_name: Sikora citation: ama: Schmalhorst PS, Deluweit F, Scherrers R, Heisenberg C-PJ, Sikora MK. Overcoming the limitations of the MARTINI force field in simulations of polysaccharides. Journal of Chemical Theory and Computation. 2017;13(10):5039-5053. doi:10.1021/acs.jctc.7b00374 apa: Schmalhorst, P. S., Deluweit, F., Scherrers, R., Heisenberg, C.-P. J., & Sikora, M. K. (2017). Overcoming the limitations of the MARTINI force field in simulations of polysaccharides. Journal of Chemical Theory and Computation. American Chemical Society. https://doi.org/10.1021/acs.jctc.7b00374 chicago: Schmalhorst, Philipp S, Felix Deluweit, Roger Scherrers, Carl-Philipp J Heisenberg, and Mateusz K Sikora. “Overcoming the Limitations of the MARTINI Force Field in Simulations of Polysaccharides.” Journal of Chemical Theory and Computation. American Chemical Society, 2017. https://doi.org/10.1021/acs.jctc.7b00374. ieee: P. S. Schmalhorst, F. Deluweit, R. Scherrers, C.-P. J. Heisenberg, and M. K. Sikora, “Overcoming the limitations of the MARTINI force field in simulations of polysaccharides,” Journal of Chemical Theory and Computation, vol. 13, no. 10. American Chemical Society, pp. 5039–5053, 2017. ista: Schmalhorst PS, Deluweit F, Scherrers R, Heisenberg C-PJ, Sikora MK. 2017. Overcoming the limitations of the MARTINI force field in simulations of polysaccharides. Journal of Chemical Theory and Computation. 13(10), 5039–5053. mla: Schmalhorst, Philipp S., et al. “Overcoming the Limitations of the MARTINI Force Field in Simulations of Polysaccharides.” Journal of Chemical Theory and Computation, vol. 13, no. 10, American Chemical Society, 2017, pp. 5039–53, doi:10.1021/acs.jctc.7b00374. short: P.S. Schmalhorst, F. Deluweit, R. Scherrers, C.-P.J. Heisenberg, M.K. Sikora, Journal of Chemical Theory and Computation 13 (2017) 5039–5053. date_created: 2018-12-11T11:48:35Z date_published: 2017-10-10T00:00:00Z date_updated: 2023-09-27T10:58:45Z day: '10' department: - _id: CaHe doi: 10.1021/acs.jctc.7b00374 external_id: isi: - '000412965700036' intvolume: ' 13' isi: 1 issue: '10' language: - iso: eng main_file_link: - open_access: '1' url: https://arxiv.org/abs/1704.03773 month: '10' oa: 1 oa_version: Submitted Version page: 5039 - 5053 publication: Journal of Chemical Theory and Computation publication_identifier: issn: - '15499618' publication_status: published publisher: American Chemical Society publist_id: '6847' quality_controlled: '1' scopus_import: '1' status: public title: Overcoming the limitations of the MARTINI force field in simulations of polysaccharides type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 13 year: '2017' ...