Size and topology modulate the effects of frustration in protein folding

Proceedings of the National Academy of Sciences of the United States of America
Alex KluberC Clementi

Abstract

The presence of conflicting interactions, or frustration, determines how fast biomolecules can explore their configurational landscapes. Recent experiments have provided cases of systems with slow reconfiguration dynamics, perhaps arising from frustration. While it is well known that protein folding speed and mechanism are strongly affected by the protein native structure, it is still unknown how the response to frustration is modulated by the protein topology. We explore the effects of nonnative interactions in the reconfigurational and folding dynamics of proteins with different sizes and topologies. We find that structural correlations related to the folded state size and topology play an important role in determining the folding kinetics of proteins that otherwise have the same amount of nonnative interactions. In particular, we find that the reconfiguration dynamics of α-helical proteins are more susceptible to frustration than β-sheet proteins of the same size. Our results may explain recent experimental findings and suggest that attempts to measure the degree of frustration due to nonnative interactions might be more successful with α-helical proteins.

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Citations

Dec 12, 2020·Soft Matter·Amir JangizehiSebastian Seiffert
Dec 6, 2019·Current Opinion in Structural Biology·Robert B Best
Feb 18, 2020·Biophysical Journal·Daniel Trotter, Stefan Wallin
Jun 1, 2021·The Journal of Physical Chemistry. a·Shubin Liu, Chunying Rong
Nov 9, 2018·The Journal of Physical Chemistry. B·Fernando Bruno da SilvaVitor B P Leite
Mar 27, 2019·Journal of the American Chemical Society·Abe D PressmanIrene A Chen
Jul 2, 2020·ACS Central Science·Maziar HeidariAlireza Mashaghi
Sep 22, 2020·The Journal of Physical Chemistry. B·Sandhyaa SubramanianAthi N Naganathan

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