Markov state models and tICA reveal a nonnative folding nucleus in simulations of NuG2

Christian R. Schwantes, Diwakar Shukla, Vijay S. Pande

Research output: Contribution to journalArticlepeer-review

Abstract

After reanalyzing simulations of NuG2 - a designed mutant of protein G - generated by Lindorff-Larsen et al. with time structure-based independent components analysis and Markov state models as well as performing 1.5 ms of additional sampling on Folding@home, we found an intermediate with a register-shift in one of the β-sheets that was visited along a minor folding pathway. The minor folding pathway was initiated by the register-shifted sheet, which is composed of solely nonnative contacts, suggesting that for some peptides, nonnative contacts can lead to productive folding events. To confirm this experimentally, we suggest a mutational strategy for stabilizing the register shift, as well as an infrared experiment that could observe the nonnative folding nucleus.

Original languageEnglish (US)
Pages (from-to)1716-1719
Number of pages4
JournalBiophysical journal
Volume110
Issue number8
DOIs
StatePublished - Apr 26 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics

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