---
_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'
...