TUTCRIS - Tampereen teknillinen yliopisto

TUTCRIS

Urea and guanidinium induced denaturation of a Trp-cage miniprotein

Tutkimustuotosvertaisarvioitu

Yksityiskohdat

AlkuperäiskieliEnglanti
Sivut8910-8924
Sivumäärä15
JulkaisuJournal of Physical Chemistry Part B
Vuosikerta115
Numero28
DOI - pysyväislinkit
TilaJulkaistu - 21 heinäkuuta 2011
OKM-julkaisutyyppiA1 Alkuperäisartikkeli

Tiivistelmä

Using a combination of experimental techniques (circular dichroism, differential scanning calorimetry, and NMR) and molecular dynamics simulations, we performed an extensive study of denaturation of the Trp-cage miniprotein by urea and guanidinium. The experiments, despite their different sensitivities to various aspects of the denaturation process, consistently point to simple, two-state unfolding process. Microsecond molecular dynamics simulations with a femtosecond time resolution allow us to unravel the detailed molecular mechanism of Trp-cage unfolding. The process starts with a destabilizing proline shift in the hydrophobic core of the miniprotein, followed by a gradual destruction of the hydrophobic loop and the α-helix. Despite differences in interactions of urea vs guanidinium with various peptide moieties, the overall destabilizing action of these two denaturants on Trp-cage is very similar.