Leonie Vollmar, Rick Bebon, Julia Schimpf, Bastian Flietel, Sirin Celiksoy, Carsten Sönnichsen, Aljaž Godec, Thorsten Hugel
{"title":"多域蛋白质构象动力学记忆的无模型推断","authors":"Leonie Vollmar, Rick Bebon, Julia Schimpf, Bastian Flietel, Sirin Celiksoy, Carsten Sönnichsen, Aljaž Godec, Thorsten Hugel","doi":"10.1088/1751-8121/ad6d1e","DOIUrl":null,"url":null,"abstract":"Single-molecule experiments provide insight into the motion (conformational dynamics) of individual protein molecules. Usually, a well-defined but coarse-grained intramolecular coordinate is measured and subsequently analysed with the help of hidden Markov models to deduce the kinetics of protein conformational changes. Such approaches rely on the assumption that the microscopic dynamics of the protein evolve according to a Markov-jump process on some network. However, the manifestation and extent of memory in the dynamics of the observable strongly depends on the chosen underlying Markov model, which is generally not known and therefore can lead to misinterpretations. Here, we combine extensive single-molecule plasmon ruler experiments on the heat shock protein Hsp90, computer simulations, and theory to infer and quantify memory in a model-free fashion. Our analysis is based on the bare definition of non-Markovian behaviour and does not require any underlying model. In the case of Hsp90 probed by a plasmon ruler, the Markov assumption is found to be clearly and conclusively violated on timescales up to roughly 50 s, which corresponds roughly to ∼50% of the inferred correlation time of the signal. The extent of memory is striking and reaches biologically relevant timescales. This implies that memory effects penetrate even the slowest observed motions. We provide clear and reproducible guidelines on how to test for the presence and duration of memory in experimental single-molecule data.","PeriodicalId":16763,"journal":{"name":"Journal of Physics A: Mathematical and Theoretical","volume":"3 1","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Model-free inference of memory in conformational dynamics of a multi-domain protein\",\"authors\":\"Leonie Vollmar, Rick Bebon, Julia Schimpf, Bastian Flietel, Sirin Celiksoy, Carsten Sönnichsen, Aljaž Godec, Thorsten Hugel\",\"doi\":\"10.1088/1751-8121/ad6d1e\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Single-molecule experiments provide insight into the motion (conformational dynamics) of individual protein molecules. Usually, a well-defined but coarse-grained intramolecular coordinate is measured and subsequently analysed with the help of hidden Markov models to deduce the kinetics of protein conformational changes. Such approaches rely on the assumption that the microscopic dynamics of the protein evolve according to a Markov-jump process on some network. However, the manifestation and extent of memory in the dynamics of the observable strongly depends on the chosen underlying Markov model, which is generally not known and therefore can lead to misinterpretations. Here, we combine extensive single-molecule plasmon ruler experiments on the heat shock protein Hsp90, computer simulations, and theory to infer and quantify memory in a model-free fashion. Our analysis is based on the bare definition of non-Markovian behaviour and does not require any underlying model. In the case of Hsp90 probed by a plasmon ruler, the Markov assumption is found to be clearly and conclusively violated on timescales up to roughly 50 s, which corresponds roughly to ∼50% of the inferred correlation time of the signal. The extent of memory is striking and reaches biologically relevant timescales. This implies that memory effects penetrate even the slowest observed motions. We provide clear and reproducible guidelines on how to test for the presence and duration of memory in experimental single-molecule data.\",\"PeriodicalId\":16763,\"journal\":{\"name\":\"Journal of Physics A: Mathematical and Theoretical\",\"volume\":\"3 1\",\"pages\":\"\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-08-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Physics A: Mathematical and Theoretical\",\"FirstCategoryId\":\"101\",\"ListUrlMain\":\"https://doi.org/10.1088/1751-8121/ad6d1e\",\"RegionNum\":3,\"RegionCategory\":\"物理与天体物理\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHYSICS, MATHEMATICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Physics A: Mathematical and Theoretical","FirstCategoryId":"101","ListUrlMain":"https://doi.org/10.1088/1751-8121/ad6d1e","RegionNum":3,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHYSICS, MATHEMATICAL","Score":null,"Total":0}
Model-free inference of memory in conformational dynamics of a multi-domain protein
Single-molecule experiments provide insight into the motion (conformational dynamics) of individual protein molecules. Usually, a well-defined but coarse-grained intramolecular coordinate is measured and subsequently analysed with the help of hidden Markov models to deduce the kinetics of protein conformational changes. Such approaches rely on the assumption that the microscopic dynamics of the protein evolve according to a Markov-jump process on some network. However, the manifestation and extent of memory in the dynamics of the observable strongly depends on the chosen underlying Markov model, which is generally not known and therefore can lead to misinterpretations. Here, we combine extensive single-molecule plasmon ruler experiments on the heat shock protein Hsp90, computer simulations, and theory to infer and quantify memory in a model-free fashion. Our analysis is based on the bare definition of non-Markovian behaviour and does not require any underlying model. In the case of Hsp90 probed by a plasmon ruler, the Markov assumption is found to be clearly and conclusively violated on timescales up to roughly 50 s, which corresponds roughly to ∼50% of the inferred correlation time of the signal. The extent of memory is striking and reaches biologically relevant timescales. This implies that memory effects penetrate even the slowest observed motions. We provide clear and reproducible guidelines on how to test for the presence and duration of memory in experimental single-molecule data.
期刊介绍:
Publishing 50 issues a year, Journal of Physics A: Mathematical and Theoretical is a major journal of theoretical physics reporting research on the mathematical structures that describe fundamental processes of the physical world and on the analytical, computational and numerical methods for exploring these structures.