--- _id: '3408' abstract: - lang: eng text: Mechanical forces govern physiological processes in all living organisms. Many cellular forces, for example, those generated in cyclic conformational changes of biological machines, have repetitive components. In apparent contrast, little is known about how dynamic protein structures respond to periodic mechanical information. Ubiquitin is a small protein found in all eukaryotes. We developed molecular dynamics simulations to unfold single and multimeric ubiquitins with periodic forces. By using a coarse-grained representation, we were able to model forces with periods about 2 orders of magnitude longer than the protein's relaxation time. We found that even a moderate periodic force weakened the protein and shifted its unfolding pathways in a frequency- and amplitude-dependent manner. A complex dynamic response with secondary structure refolding and an increasing importance of local interactions was revealed. Importantly, repetitive forces with broadly distributed frequencies elicited very similar molecular responses compared to fixed-frequency forces. When testing the influence of pulling geometry on ubiquitin's mechanical stability, it was found that the linkage involved in the mechanical degradation of cellular proteins renders the protein remarkably insensitive to periodic forces. We also devised a complementary kinetic energy landscape model that traces these observations and explains periodic-force, single-molecule measurements. In turn, this analytical model is capable of predicting dynamic protein responses. These results provide new insights into ubiquitin mechanics and a potential mechanical role during protein degradation, as well as first frameworks for dynamic protein stability and the modeling of repetitive mechanical processes. author: - first_name: Piotr full_name: Szymczak, Piotr last_name: Szymczak - first_name: Harald L full_name: Harald Janovjak id: 33BA6C30-F248-11E8-B48F-1D18A9856A87 last_name: Janovjak orcid: 0000-0002-8023-9315 citation: ama: Szymczak P, Janovjak HL. Periodic forces trigger a complex mechanical response in ubiquitin. Journal of Molecular Biology. 2009;390(3):443-456. doi:10.1016/j.jmb.2009.04.071 apa: Szymczak, P., & Janovjak, H. L. (2009). Periodic forces trigger a complex mechanical response in ubiquitin. Journal of Molecular Biology. Elsevier. https://doi.org/10.1016/j.jmb.2009.04.071 chicago: Szymczak, Piotr, and Harald L Janovjak. “Periodic Forces Trigger a Complex Mechanical Response in Ubiquitin.” Journal of Molecular Biology. Elsevier, 2009. https://doi.org/10.1016/j.jmb.2009.04.071. ieee: P. Szymczak and H. L. Janovjak, “Periodic forces trigger a complex mechanical response in ubiquitin,” Journal of Molecular Biology, vol. 390, no. 3. Elsevier, pp. 443–456, 2009. ista: Szymczak P, Janovjak HL. 2009. Periodic forces trigger a complex mechanical response in ubiquitin. Journal of Molecular Biology. 390(3), 443–456. mla: Szymczak, Piotr, and Harald L. Janovjak. “Periodic Forces Trigger a Complex Mechanical Response in Ubiquitin.” Journal of Molecular Biology, vol. 390, no. 3, Elsevier, 2009, pp. 443–56, doi:10.1016/j.jmb.2009.04.071. short: P. Szymczak, H.L. Janovjak, Journal of Molecular Biology 390 (2009) 443–456. date_created: 2018-12-11T12:03:10Z date_published: 2009-07-17T00:00:00Z date_updated: 2021-01-12T07:43:16Z day: '17' doi: 10.1016/j.jmb.2009.04.071 extern: 1 intvolume: ' 390' issue: '3' month: '07' page: 443 - 456 publication: Journal of Molecular Biology publication_status: published publisher: Elsevier publist_id: '2994' quality_controlled: 0 status: public title: Periodic forces trigger a complex mechanical response in ubiquitin type: journal_article volume: 390 year: '2009' ...