title: Position-dependent effects of fluorinated amino acids on the hydrophobic core formation of a heterodimeric coiled coil.
abstract: Systematic model investigations of the molecular interactions of fluorinated amino acids within native protein environments substantially improve our understanding of the unique properties of these building blocks. A rationally designed heterodimeric coiled coil peptide (VPE/VPK) and nine variants containing amino acids with variable fluorine content in either position a16 or d19 within the hydrophobic core were synthesized and used to evaluate the impact of fluorinated amino acid substitutions within different hydrophobic protein microenvironments. The structural and thermodynamic stability of the dimers were examined by applying both experimental (CD spectroscopy, FRET, and analytical ultracentrifugation) and theoretical (MD simulations and MM-PBSA free energy calculations) methods. The coiled coil environment imposes position-dependent conformations onto the fluorinated side chains and thus affects their packing and relative orientation towards their native interaction partners. We find evidence that such packing effects exert a significant influence on the contribution of fluorine-induced polarity to coiled coil folding.
authors: Department of Biology, Chemistry, and Pharmacy, Freie Universiät Berlin, Institute of Chemistry and Biochemistry-Organic Chemistry, Takustrasse 3, 14195 Berlin, Germany.
authors: Mario
authors: M
authors: Salwiczek
authors: Sergey
authors: S
authors: Samsonov
authors: Toni
authors: T
authors: Vagt
authors: Elisabeth
authors: E
authors: Nyakatura
authors: Emanuel
authors: E
authors: Fleige
authors: Jorge
authors: J
authors: Numata
authors: Helmut
authors: H
authors: Cölfen
authors: M Teresa
authors: MT
authors: Pisabarro
authors: Beate
authors: B
authors: Koksch
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D006845:Hydrocarbons, Fluorinated; D011506:Proteins