Sequential protein unfolding through a carbon nanotube pore

Area of Science:

• Biophysics
• Computational Biology
• Materials Science

Background:

• Protein unfolding is crucial for biological processes like degradation and transport.
• Nanopore interfaces play a role in mediating these unfolding events.

Purpose of the Study:

• Investigate the unfolding behavior of ubiquitin using atomistic simulations.
• Characterize the role of a carbon nanotube (CNT)-based nanopore in protein unfolding.

Main Methods:

• Fully atomistic simulations of ubiquitin being pulled through a CNT nanopore.
• Application of external force to one end of the protein.

Main Results:

• Observed non-canonical unfolding where secondary structures detach sequentially and thread into the nanotube.
• Identified stable "unfoldon" motifs formed at the nanopore interface.
• Destruction of unfoldons generated distinct force peaks, serving as probes for unfolding kinetics.

Conclusions:

• Nanopore interfaces can facilitate the formation of stable intermediate structures during protein unfolding.
• These findings provide insights into cellular protein unfolding mechanisms and protein conformational stability.