Alpha-hairpin stability and folding of transmembrane segments.
Molecular Dynamics (MD) simulations at low dielectric constant have been carried out for peptides matching the double spanning segments of transmembrane proteins. Different folding dynamics have been observed. The peptides folded into the stable helix-turn-helix conformation-alpha-hairpin-with antiparallel-oriented strands or unstable alpha-hairpin conformation that unfolded later into the straight helical structure. The peptide having flexible residues in the TM helices often misfolded into a tangled structure that can be avoided by restricting the flexibility of these residues. General conclusions can be drawn from the observed folding dynamics. The stability and folding of some double spanning transmembrane fragments are self-assembling. The following and/or neighboring peptide chains of the protein may support the stability of the hairpin structure of other fragments. The stability of the TM helices containing flexible residues could be maintained due to contacts with neighboring TM segments.
Khutorsky
Vitaly
V
CIHR Group In Membrane Biology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8. vitaly.khutorsky@utoronto.ca
D003198:Computer Simulation; D008562:Membrane Glycoproteins / Q000737:chemistry; D008958:Models, Molecular; D009004:Monosaccharide Transport Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051269:Sodium-Glucose Transporter 1
D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D010455:Peptides; D051269:Sodium-Glucose Transporter 1