Funneling and frustration in the energy landscapes of some designed and simplified proteins
Author
Truong, Ha H.
Kim, Bobby L.
Schafer, Nicholas P.
Wolynes, Peter G.
Date
2013Citation
Published Version
Abstract
We explore the similarities and differences between the energy landscapes of proteins that have been
selected by nature and those of some proteins designed by humans. Natural proteins have evolved
to function as well as fold, and this is a source of energetic frustration. The sequence of Top7, on
the other hand, was designed with architecture alone in mind using only native state stability as the
optimization criterion. Its topology had not previously been observed in nature. Experimental studies
show that the folding kinetics of Top7 is more complex than the kinetics of folding of otherwise
comparable naturally occurring proteins. In this paper, we use structure prediction tools, frustration
analysis, and free energy profiles to illustrate the folding landscapes of Top7 and two other proteins
designed by Takada. We use both perfectly funneled (structure-based) and predictive (transferable)
models to gain insight into the role of topological versus energetic frustration in these systems and
show how they differ from those found for natural proteins. We also study how robust the folding
of these designs would be to the simplification of the sequences using fewer amino acid types. Simplification
using a five amino acid type code results in comparable quality of structure prediction to
the full sequence in some cases, while the two-letter simplification scheme dramatically reduces the
quality of structure prediction.
Type
Journal article
Citable link to this page
http://hdl.handle.net/1911/71717Metadata
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