TY  - JOUR
AU  - Owen, Michael C.
AU  - Strodel, Birgit
AU  - Csizmadia, Imre G.
AU  - Viskolcz, Béla
TI  - Radical Formation Initiates Solvent-Dependent Unfolding and β-Sheet Formation in a Model Helical Peptide
JO  - The journal of physical chemistry  / B
VL  - 120
IS  - 22
SN  - 1520-5207
CY  - Washington, DC
PB  - Soc.
M1  - FZJ-2016-06506
SP  - 4878 - 4889
PY  - 2016
AB  - We examined the effects of Cα-centered radical formation on the stability of a model helical peptide, N-Ac-KK(AL)10KK-NH2. Three, 100 ns molecular dynamics simulations using the OPLS-AA force field were carried out on each α-helical peptide in six distinct binary TIP4P water/2,2,2-trifluoroethanol (TFE) mixtures. The α-helicity was at a maximum in 20% TFE, which was inversely proportional to the number of H-bonds between water molecules and the peptide backbone. The radial distribution of TFE around the peptide backbone was highest in 20% TFE, which enhanced helix stability. The Cα-centered radical initiated the formation of a turn within 5 ns, which was a smaller kink at high TFE concentrations, and a loop at lower TFE concentrations. The highest helicity of the peptide radical was measured in 100% TFE. The formation of hydrogen bonds between the peptide backbone and water destabilized the helix, whereas the clustering of TFE molecules around the radical center stabilized the helix. Following radical termination, the once helical structure converted to a β-sheet rich state in 100% water only, and this transition did not occur in the nonradical control peptide. This study gives evidence on how the formation of peptide radicals can initiate α-helical to β-sheet transitions under oxidative stress conditions.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000377841200002
C6  - pmid:27169334
DO  - DOI:10.1021/acs.jpcb.6b00174
UR  - https://juser.fz-juelich.de/record/823866
ER  -