Understanding the structural and dynamic information encoded in the primary sequence of a protein is one of the most fundamental challenges in modern biology. The amino acid sequence of a protein encodes more than the native three-dimensional structure; it encodes the entire energy landscape – an ensemble of conformations whose energetics and dynamics are finely tuned for folding, binding and activity. Small variations in the sequence and environment modulate this landscape and can have effects that range from undetectable to pathological.<br/>I will present our recent results probing these sequence and environmental effects using a combination of single-molecule and ensemble-based studies. I will address a fundamental question in protein folding of whether proteins fold through one or multiple trajectories. By using a combination of chemical denaturant, mechanical force, we find multiple unfolding pathways in a simple, two-state folding protein; the dominant pathway can be altered by small changes in the sequence or environment. I will explore the implications of this result for 1) protein folding in complex environments, such as in the cell, or on the ribosome, and 2) the suggestion that evolution can modulate both the rates of folding and the specific pathway.

Touring the protein folding landscape: The view depends on how and where you look

253rd National Meeting (2017)

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