Abstract
Biological processes are carried out through conformational transitions, ranging from the structural changes within biomolecules to the formation of macromolecular complexes and the associations between the complexes themselves. These transitions cover a vast range of timescales and are governed by a tangled network of molecular interactions. The resulting hierarchy of interactions, in turn, becomes encoded in the experimentally measurable "mechanical fingerprints" of the biomolecules, their force-extension curves. How can we decode these fingerprints so that they reveal the kinetic barriers and the associated timescales of a biological process? Here, we show [1] that this can be accomplished with a simple, model-free transformation that is general enough to be applicable to molecular interactions involving an arbitrarily large number of barriers. Specifically, the transformation converts the mechanical fingerprints of the system directly into a map of force-dependent rate constants. This map reveals the kinetics of the multitude of rate processes beyond what is typically accessible to direct measurements. With the contributions from individual barriers to the interaction network now "untangled", the map is straightforward to analyze in terms of the barriers and timescales. [1] Y. Zhang and O.K. Dudko, PNAS 2013, doi:10.1073/pnas.1309101110.
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