Glycine Shows Preference for Polyproline II Indicating Greater Role for Amino Acid Backbone

Amino acid residues exhibit conformational preferences in water and it is still unclear whether the preferences are attributed to properties of the amino acid backbone or side chain. A glycine-based peptide, which lacks a heavy-atom side chain, is a good model for examining the potential role of the backbone in amino acid conformational preferences. In this work, triglycine (GGG), which is intrinsically disordered due to its short length, is simulated using three commonly used Molecular Dynamic (MD) force fields. The central glycine of GGG is analyzed and compared to previously published spectroscopic data which demonstrates pPII is the dominant state in the conformational ensemble. The pPII propensity of the central glycine is comparable to that of the central alanine in GAG which implies the backbone is responsible for high pPII content. Further analysis shows that backbone-water hydrogen bonding is the mechanism that promotes this preference and pPII is less prevalent when GGG is immersed in solvents with limited hydrogen bonding capabilities. [B. Andrews, S. Zhang, R. Schweitzer-Stenner, and B. Urbanc, Glycine in Water Favors the Polyproline II State, Biomolecules 10, 1121 (2020)]