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Position‐Dependent Effects of Fluorinated Amino Acids on the Hydrophobic Core Formation of a Heterodimeric Coiled Coil
Author(s) -
Salwiczek Mario,
Samsonov Sergey,
Vagt Toni,
Nyakatura Elisabeth,
Fleige Emanuel,
Numata Jorge,
Cölfen Helmut,
Pisabarro M. Teresa,
Koksch Beate
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200802136
Subject(s) - amino acid , coiled coil , chemistry , hydrophobic effect , folding (dsp implementation) , side chain , peptide , affinities , biophysics , crystallography , stereochemistry , combinatorial chemistry , organic chemistry , biochemistry , polymer , electrical engineering , biology , engineering
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.