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Author Szymczak, Piotr ♦ Janovjak, Harald
Source CiteSeerX
Content type Text
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Subject Domain (in DDC) Computer science, information & general works ♦ Data processing & computer science
Abstract Mechanical forces govern physiological processes in all living organisms. Many cellular forces, e.g. 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 two 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.
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Research
Education Level UG and PG ♦ Career/Technical Study