Studying cotranslational protein folding by experiment is challenging because of the difficulty of synchronizing measurements across a population of ribosomes. The use of arrest peptides, which, when included in a translating sequence, cause a temporary pause in translation via a physical obstruction near the peptidyl transfer center, provide a valuable tool for investigating folding. One of their most intriguing applications has been in measuring the forces exerted by the nascent polypeptide as it attempts to fold -- however, the forces were originally indirectly inferred by measuring the fraction of peptide escaping arrest via thermal fluctuations during a fixed time period. In our work, we have developed coarse-grained models which can be used, together with suitable kinetic models, can be used to interpret the yield of protein escaping arrest in terms of the forces exerted by the nascent chain as it attempts to fold. We have also developed models for more directly interpreting the protein yield in terms of forces without the need for doing simulations.

Quantifying forces exerted by proteins during cotranslational folding using coarse-grained simulations

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