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Markov State Models and tICA Reveal a Nonnative Folding Nucleus in Simulations of NuG2.

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 ?-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.

SUBMITTER: Schwantes CR

PROVIDER: S-EPMC4850345 | biostudies-other | 2016 Apr

REPOSITORIES: biostudies-other

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Markov State Models and tICA Reveal a Nonnative Folding Nucleus in Simulations of NuG2.

Schwantes Christian R CR Shukla Diwakar D Pande Vijay S VS

Biophysical journal 20160401 8

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, suggest ...[more]

PMID: 27119632

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