Compact folding of isolated four-residue neutral peptide chains: H-bonding patterns and entropy effects.

The intrinsic folding of isolated neutral tetrapeptides is investigated by IR-UV double-resonance laser spectroscopy coupled to quantum chemistry (DFT-D) calculations. Laser-desorbed jet-cooled Ac-(Ala)(3)-Phe-NH(2) as well as two other related four-residue molecules are shown to fold according to the same 14-7L-X-10II'-7L compact, β-hairpin-like backbone pattern, leading to a remarkable closed daisy chain of H-bonds along the molecule. Thermodynamic calculations confronted to the abundances observed show that these laser-desorbed peptides are best described by a finite conformational temperature (typically ca. 300-450 K), which suggests that not only enthalpy but also entropy effects play an important role in selecting these structures within this temperature range.