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In Vitro Analysis of E3 Ubiquitin Ligase Function
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Picosecond to Millisecond Structural Dynamics in Human Ubiquitin.
Kresten Lindorff-Larsen1, Paul Maragakis1, Stefano Piana1
1D. E. Shaw Research , New York, New York 10036, United States.
The Journal of Physical Chemistry. B
|April 16, 2016
Summary
Human ubiquitin dynamics were simulated from picoseconds to milliseconds. Unbiased simulations reveal distinct protein states and correlated motions, aiding future experimental interpretations.
Area of Science:
- Biophysics
- Computational Biology
- Structural Biology
Background:
- Human ubiquitin is a model protein for studying protein dynamics.
- Characterizing ubiquitin's microsecond timescale dynamics at atomistic resolution remains challenging.
Purpose of the Study:
- To describe the structural dynamics of ubiquitin on the picosecond to millisecond timescale using unbiased computer simulations.
- To provide a detailed atomistic description of ubiquitin dynamics for interpreting experimental data.
Main Methods:
- Unbiased computer simulations.
- Atomistic resolution molecular dynamics simulations covering picosecond to millisecond timescales.
Main Results:
- Ubiquitin interconverts between a small number of distinct states on the microsecond to millisecond timescale.
- Free ubiquitin conformations in solution closely resemble those in crystal structures.
- Weak but statistically significant correlated motions, including long-range concerted movement across the beta sheet, were observed.
Conclusions:
- Unbiased simulations provide valuable insights into ubiquitin's dynamic behavior.
- The findings align with and support previous experimental observations.
- This detailed simulation data can aid in the interpretation of current and future ubiquitin-related experiments.
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