pH-dependent structural dynamics of neuropeptide Y in aqueous solution

Area of Science:

• Neuroscience
• Biochemistry
• Computational Biology

Background:

• Neuropeptide Y (NPY) is a key regulator of brain molecular processes.
• NPY interacts with cell membrane receptors, influencing physiological functions.
• Previous structural studies were limited to acidic pH, leaving protonation states and dynamics at physiological pH unexplored.

Purpose of the Study:

• To investigate the pH-dependent dynamics and hydrogen bond patterns of Neuropeptide Y.
• To explore the interplay between residue protonation states and peptide conformational changes.
• To determine the structural behavior of NPY across a physiologically relevant pH range (3.0-7.0).

Main Methods:

• Constant pH molecular dynamics simulations.
• Graph-based analyses of peptide dynamics and hydrogen bonding.
• Exploration of protonation states for carboxylic and histidine residues.

Main Results:

• Neuropeptide Y consistently exhibits an alpha-helical core across the studied pH range.
• The length of the alpha-helix varies by 2-3 residues depending on the pH.
• Significant shifts in pKa values were observed for Asp16 and Asp11, potentially exceeding one pH unit.

Conclusions:

• Constant pH simulations are essential for accurately modeling Neuropeptide Y structure and dynamics.
• Understanding pH-dependent conformational changes is critical for describing NPY interactions with its cellular partners.
• The findings highlight the need to consider pH in future studies of Neuropeptide Y function.