title: NMR study and molecular dynamics simulations of optimized beta-hairpin fragments of protein G.
abstract: The stability and structure of several beta-hairpin peptide variants derived from the C-terminus of the B1 domain of protein G were investigated by a number of experimental and computational techniques. Our analysis shows that the structure and stability of this hairpin can be greatly affected by one or a few simple mutations. For example, removing an unfavorable charge near the N-terminus of the peptide (Glu42 to Gln or Thr) or optimization of the N-terminal charge-charge interactions (Gly41 to Lys) both stabilize the peptide, even in water. Furthermore, a simple replacement of a charged residue in the turn (Asp47 to Ala) changes the beta-turn conformation. Finally, we show that the effects of combining these single mutations are additive, suggesting that independent stabilizing interactions can be isolated and evaluated in a simple model system. Our results indicate that the structure and stability of this beta-hairpin peptide can be modulated in numerous ways and thus contributes toward a more complete understanding of this important model beta-hairpin as well as to the folding and stability of larger peptides and proteins.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wei
authors.forename: Beatrice M P
authors.initials: BM
authors.lastname: Huyghues-Despointes
authors.forename: Jerry
authors.initials: J
authors.lastname: Tsai
authors.forename: J Martin
authors.initials: JM
authors.lastname: Scholtz
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: C029152:G-substrate; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments