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The Effect of Fluoro Substitution upon the β ‐Hairpin Fold of a β ‐Tetrapeptide in Methanol
Author(s) -
Bachmann Stephan,
Jaun Bernhard,
van Gunsteren Wilfred F.,
Wang Dongqi
Publication year - 2010
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201000179
Subject(s) - chemistry , tetrapeptide , peptide , stereochemistry , molecular dynamics , crystallography , computational chemistry , biochemistry
The importance of β ‐peptides lies in their ability to mimic the conformational behavior of α ‐peptides, even with a much shorter chain length, and in their resistance to proteases. To investigate the effect of substitution of β ‐peptides on their dominant fold, we have carried out a molecular‐dynamics (MD) simulation study of two tetrapeptides, Ac‐(2 R ,3 S )‐ β 2,3 hVal( α Me)‐(2 S )‐ β 2 hPhe‐( R )‐ β 3 hLys‐(2 R ,3 S )‐ β 2,3 ‐Ala( α Me)‐NH 2 , differing in the substitution at the C α of Phe2 (pepF with F, and pepH with H). Three simulations, unrestrained (UNRES), using 3 J ‐coupling biasing with local elevation in combination with either instantaneous (INS) or time‐averaging (AVE) NOE distance restraining, were carried out for each peptide. In the unrestrained simulations, we find three (pepF) and two (pepH) NOE distance bound violations of maximally 0.22 nm that involve the terminal residues. The restrained simulations match both the NOE distance bounds and 3 J ‐values derived from experiment. The fluorinated peptide shows a slightly larger conformational variability than the non‐fluorinated one.