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Updated: Jul 9, 2026

Covalent Immobilization of Proteins for the Single Molecule Force Spectroscopy
Published on: August 20, 2018
Consequences of localized frustration for the folding mechanism of the IM7 protein
Ludovico Sutto1, Joachim Lätzer, Joseph A Hegler
1Department of Physics, University of Milan, Via Celoria 16, 20133 Milan, Italy.
In the laboratory, IM7 has been found to have an unusual folding mechanism in which an "on-pathway" intermediate with nonnative interactions is formed. We show that this intermediate is a consequence of an unusual cluster of highly frustrated interactions in the native structure. This cluster is involved in the binding of IM7 to its target, Colicin E7. Redesign of residues in this cluster to eliminate frustration is predicted by simulations to lead to faster folding without the population of an intermediate ensemble.
In the laboratory, IM7 has been found to have an unusual folding mechanism in which an "on-pathway" intermediate with nonnative interactions is formed. We show that this intermediate is a consequence of an unusual cluster of highly frustrated interactions in the native structure. This cluster is involved in the binding of IM7 to its target, Colicin E7. Redesign of residues in this cluster to eliminate frustration is predicted by simulations to lead to faster folding without the population of an intermediate ensemble.
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