Position-dependent effects of fluorinated amino acids on the hydrophobic core formation of a heterodimeric coiled coil

Mario Salwiczek, Sergey Samsonov, Toni Vagt, Elisabeth Nyakatura, Emanuel Fleige, Jorge Numata, Helmut Cölfen, M. Teresa Pisabarro, Beate Koksch

Research output: Contribution to journalArticle

37 Scopus citations

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 analyti-cal 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 part-ners. We find evidence that such packing effects exert a significant influence on the contribution of fluorine-induced polarity to coiled coil folding.

Original languageEnglish (US)
Pages (from-to)7628-7636
Number of pages9
JournalChemistry - A European Journal
Volume15
Issue number31
DOIs
Publication statusPublished - Aug 3 2009
Externally publishedYes

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Keywords

  • Amino acids
  • Fluorine
  • Helical structures
  • Molecular dynamics

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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