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Distinguishing Signatures of Multipathway Conformational Transitions.

Christopher A Pierse¹, Olga K Dudko¹

¹Department of Physics, University of California at San Diego, La Jolla, California 92093, USA.

Physical Review Letters

|March 11, 2017

Summary

Biomolecules often use multiple pathways for folding and binding, not just one. New methods reveal distinct signatures in molecular responses to force, confirming multiple pathways even when individual routes are unclear.

Area of Science:

Biophysics
Molecular Biology
Biochemistry

Background:

Biomolecular folding and binding are crucial for function.
Multiple pathways are hypothesized but difficult to prove experimentally.

Purpose of the Study:

To develop model-free methods for identifying multiple conformational pathways in biomolecules.
To analyze the impact of multiple pathways on molecular responses to force.

Main Methods:

Analysis of observable signatures in macromolecular response to force.
Model-free analytical description of molecular behavior.

Main Results:

Identified unambiguous, observable signatures for multiple pathways.
Demonstrated that multiple pathways shape molecular responses to force in diverse ways.
Revealed a rich design space for biological function at the single-molecule level.

Conclusions:

Multiple pathways are a key factor in biomolecular function.
The developed methods allow for the detection of multiple pathways without resolving them.
Understanding multiple pathways opens possibilities for designing tailored biological functions.

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