Dynamics of a type VI reverse turn in a linear peptide in aqueous solution

Area of Science:

• Biophysics
• Computational Chemistry

Background:

• Peptide sequences with aromatic groups flanking cis-proline residues favor compact structures.
• Aromatic sidechains pack against the proline ring, promoting specific conformations.
• The Ser-Tyr-Pro-Phe-Asp-Val sequence and variants form type VI turns in aqueous solution.

Purpose of the Study:

• To explore the energetic and dynamic features of aromatic-proline containing peptide sequences.
• To investigate the stability and conformational preferences of specific peptide sequences using computational methods.

Main Methods:

• Solvated molecular dynamics simulations of the pentapeptide NH3(+)-Ala-Tyr-cisPro-Tyr-Asp-NMA (cis-AYPYD).
• Simulations initiated from NMR-derived structures and extended conformations.
• Analysis of conformational transitions, turn types (VIa and VIb), and sidechain interactions.

Main Results:

• The cis-AYPYD peptide demonstrated transitions between type VIa and VIb turns but maintained folded conformations.
• Simulated peptide structures showed good agreement with experimental NMR data (Nuclear Overhauser peaks, sidechain rotamer populations).
• Spontaneous folding from extended to NMR-like structures was observed within 3 ns in one simulation.

Conclusions:

• The kinetic stability of folded cis-AYPYD forms is consistent with experimental observations.
• Aromatic-proline interactions significantly stabilize peptide secondary structures.
• Computer simulations provide insights into the interconversion pathways of type VIa and VIb turns.