Nascent β-Hairpin Formation of a Natively Unfolded Peptide Reveals the Role of Hydrophobic Contacts.

ABSTRACT: Despite the important role of the unfolded states in protein stability, folding, and aggregation, they remain poorly understood due to the lack of residue-specific experimental data. Here, we explore features of the unfolded state of the NTL9 protein by applying all-atom replica-exchange simulations to the two fragment peptides NTL9(1-22) and NTL9(6-17). We found that while NTL9(6-17) is unstructured, NTL9(1-22) transiently folds as various β-hairpins, a fraction of which contain a native β-sheet. Interestingly, despite a large number of charged residues, the formation of backbone hydrogen bonds is concomitant with hydrophobic but not electrostatic contacts. Although the fragment peptides lack a proposed specific contact between Asp(8) and Lys(12), the individually weak, nonspecific intera

SUBMITTER: Chen W 

PROVIDER: S-EPMC4571001 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature