{"abstract":[{"text":"Probing reaction mechanisms of supramolecular processes in soft and biological matter, such as protein aggregation, is inherently challenging. This is because these processes involve multiple molecular mechanisms that are associated with the rearrangement of large numbers of weak bonds, resulting in complex free energy landscapes with many kinetic barriers. Reaction rate measurements at different temperatures can offer unprecedented insights into the underlying molecular mechanisms. However, to be able to interpret such measurements, a key challenge is to establish which properties of the complex free energy landscapes are probed by the reaction rate. Here, we present a reaction rate theory for supramolecular kinetics based on Kramers theory of diffusive reactions over multiple kinetic barriers. We find that reaction rates for protein aggregation are of the Arrhenius–Eyring type and that the associated activation energies probe only one relevant barrier along the respective free energy landscapes. We apply this advancement to interpret, in experiments and in coarse-grained computer simulations, reaction rates of amyloid aggregation in terms of molecular mechanisms and associated thermodynamic signatures. These results suggest a practical extension of the concept of rate-determining steps for complex supramolecular processes and establish a general platform for probing the underlying energy landscape using kinetic measurements.","lang":"eng"}],"publication":"Molecular Physics","publication_status":"published","doi":"10.1080/00268976.2018.1474280","author":[{"first_name":"Thomas C. T.","full_name":"Michaels, Thomas C. T.","last_name":"Michaels"},{"last_name":"Liu","full_name":"Liu, Lucie X.","first_name":"Lucie X."},{"first_name":"Samo","full_name":"Curk, Samo","last_name":"Curk"},{"last_name":"Bolhuis","first_name":"Peter G.","full_name":"Bolhuis, Peter G."},{"id":"bf63d406-f056-11eb-b41d-f263a6566d8b","last_name":"Šarić","orcid":"0000-0002-7854-2139","full_name":"Šarić, Anđela","first_name":"Anđela"},{"first_name":"Tuomas P. J.","full_name":"Knowles, Tuomas P. J.","last_name":"Knowles"}],"_id":"10358","publication_identifier":{"issn":["0026-8976"],"eissn":["1362-3028"]},"type":"journal_article","extern":"1","volume":116,"date_updated":"2021-11-26T12:39:58Z","oa":1,"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","external_id":{"arxiv":["1803.04851"]},"page":"3055-3065","status":"public","date_created":"2021-11-26T12:08:02Z","month":"05","citation":{"apa":"Michaels, T. C. T., Liu, L. X., Curk, S., Bolhuis, P. G., Šarić, A., &#38; Knowles, T. P. J. (2018). Reaction rate theory for supramolecular kinetics: application to protein aggregation. <i>Molecular Physics</i>. Taylor &#38; Francis. <a href=\"https://doi.org/10.1080/00268976.2018.1474280\">https://doi.org/10.1080/00268976.2018.1474280</a>","chicago":"Michaels, Thomas C. T., Lucie X. Liu, Samo Curk, Peter G. Bolhuis, Anđela Šarić, and Tuomas P. J. Knowles. “Reaction Rate Theory for Supramolecular Kinetics: Application to Protein Aggregation.” <i>Molecular Physics</i>. Taylor &#38; Francis, 2018. <a href=\"https://doi.org/10.1080/00268976.2018.1474280\">https://doi.org/10.1080/00268976.2018.1474280</a>.","ista":"Michaels TCT, Liu LX, Curk S, Bolhuis PG, Šarić A, Knowles TPJ. 2018. Reaction rate theory for supramolecular kinetics: application to protein aggregation. Molecular Physics. 116(21–22), 3055–3065.","ieee":"T. C. T. Michaels, L. X. Liu, S. Curk, P. G. Bolhuis, A. Šarić, and T. P. J. Knowles, “Reaction rate theory for supramolecular kinetics: application to protein aggregation,” <i>Molecular Physics</i>, vol. 116, no. 21–22. Taylor &#38; Francis, pp. 3055–3065, 2018.","short":"T.C.T. Michaels, L.X. Liu, S. Curk, P.G. Bolhuis, A. Šarić, T.P.J. Knowles, Molecular Physics 116 (2018) 3055–3065.","ama":"Michaels TCT, Liu LX, Curk S, Bolhuis PG, Šarić A, Knowles TPJ. Reaction rate theory for supramolecular kinetics: application to protein aggregation. <i>Molecular Physics</i>. 2018;116(21-22):3055-3065. doi:<a href=\"https://doi.org/10.1080/00268976.2018.1474280\">10.1080/00268976.2018.1474280</a>","mla":"Michaels, Thomas C. T., et al. “Reaction Rate Theory for Supramolecular Kinetics: Application to Protein Aggregation.” <i>Molecular Physics</i>, vol. 116, no. 21–22, Taylor &#38; Francis, 2018, pp. 3055–65, doi:<a href=\"https://doi.org/10.1080/00268976.2018.1474280\">10.1080/00268976.2018.1474280</a>."},"article_processing_charge":"No","acknowledgement":"We thank Claudia Flandoli for the help with illustrations.","oa_version":"Preprint","issue":"21-22","title":"Reaction rate theory for supramolecular kinetics: application to protein aggregation","scopus_import":"1","quality_controlled":"1","main_file_link":[{"url":"https://arxiv.org/abs/1803.04851","open_access":"1"}],"language":[{"iso":"eng"}],"intvolume":"       116","date_published":"2018-05-24T00:00:00Z","day":"24","publisher":"Taylor & Francis","article_type":"original","year":"2018","keyword":["physical chemistry"]}