A Transformation for the Mechanical Fingerprints of Complex Biomolecular Interactions
Yaojun Zhang
Department of Physics and Center for Theoretical Biological Physics
UC San Diego
ABSTRACT
Biological processes are carried out through molecular
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. However, how can we
decode these fingerprints so that they reveal the kinetic barriers and the
associated timescales of a biological process? Here, we show 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 kinetic 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 in the system 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 prominent barriers and
timescales. Practical implementation of the transformation is illustrated
with simulated biomolecular interactions that comprise different patterns
of complexity---from a cascade of activation barriers to competing
dissociation pathways.
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