Folding, dynamics and interaction studies of the Neuropeptide Y family.

Abstract

Detailed molecular knowledge of the complex dynamics of biological processes such as folding and the interaction with cellular membranes may greatly advance the treatment of human disease. The Neuropeptide Y family of peptides are highly conserved peptides found in nature, consist of 36 amino acids, and are widely distributed in the central nervous system of mammals. A detailed study of thermodynamics, kinetics, membrane translocation, and receptor interaction of human neuropeptide Y (NPY) and the thermodynamics and detailed molecular modeling of human peptide YY (PYY) were investigated. These studies employed a combination of experiment and simulation to characterize the two most important members of the neuropeptide Y family. The formation of secondary structures is one of the most fundamental processes in protein folding. To obtain a detailed understanding of protein folding it is useful to study peptide models that provide well defined stable structures in solution. NPY and PYY are composed primarily of two important secondary structural elements: the α-helix and hairpin-like structure. Therefore, further analysis of the three most prevalent helical secondary structures found in nature (α-, 3₁₀-, π-helix) and the β-hairpin structure were carried out with carefully designed peptide models to characterize their individual structures and formation. These studies suggest two different mechanisms of formation for helical and β-hairpin structures.