English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Experimentally, protein engineering and phi-value analysis is the method of choice to characterize the structure in folding transition state ensemble (TSE) of any protein. Combining experimental phi values and computer simulations has led to a deeper understanding of how proteins fold. In this report, we construct the TSE of chymotrypsin inhibitor 2 from published phi values. Importantly, we verify, by means of multiple independent simulations, that the conformations in the TSE have a probability of approximately 0.5 to reach the native state rapidly, so the TSE consists of true transition states. This finding validates the use of transition state theory underlying all phi-value analyses. Also, we present a method to dissect and study the TSE by generating conformations that have a disrupted alpha-helix (alpha-disrupted states) or disordered beta-strands 3 and 4 (beta-disrupted states). Surprisingly, the alpha-disrupted states have a stronger tendency to fold than the beta-disrupted states, despite the higher phi values for the alpha-helix in the TSE. We give a plausible explanation for this result and discuss its implications on protein folding and design. Our study shows that, by using both experiments and computer simulations, we can gain many insights into protein folding.

Constructing, verifying, and dissecting the folding transition state of chymotrypsin inhibitor 2 with all-atom simulations