Figure 3.

The diverse physicochemical properties of neuropeptides. (A) Pair plot comparing the molecular weight (kDa), theoretical net charge at a physiologic pH of 7.4, and the Potential Protein Interaction Index (PPI-Index), a predictor of a polypeptide’s propensity to bind other proteins/receptors,⁴⁹ for all 283 human neuropeptides in the NeuroPep database.⁴⁸ The properties were estimated from the peptide sequences using the peptides.py package (https://github.com/althonos/peptides.py).⁵⁰ Note that the diagonal edge of the pair plot shows the distributions of each property. (B) A selection of human neuropeptide structures collected from the RCSB Protein Data Bank⁵¹ and AlphaFold Protein Structure Database^{52, 53} highlighting the diversity of neuropeptide structure and physicochemical properties, including the 38 amino acid variant (blue) of pituitary adenylate cyclase-activating peptide (PACAP), Neuropeptide Y (red), glucagon (green), the 27 amino acid variant of PACAP (orange), Somatostatin 14 (light blue), and Dynorphin A (1-13) (yellow). The neuropeptide structures were rendered using the Visual Molecular Dynamics (VMD) software.⁵⁴