Interplay of Amino Acid Sequence, Intrinsic Folding Propensity, and Solvent Effects in Shaping Peptide Secondary Structures and their Functional Implications. – ( Aloke Das/ LCAR / Seminar). – 18/06/2026, 11H

Séminaire LCAR

Aloke Das, Department of Chemistry, Indian Institute of Science Education and Research (IISER) Pune, India

Summary :
Secondary structures of peptides play a crucial role in shaping the overall three-dimensional architecture of proteins. The most common secondary structures found in peptides include α- helices, β-sheets, and turns. Among these, turns are especially important because they reverse the direction of polypeptide chains, thereby contributing to their compactness and stability. Turns are categorized into types such as C7 (γ-turn), C10 (β-turn), and C13 (α-turn), depending on the specific hydrogen-bonded rings formed between residues in the backbone. Given that these structures are fundamentally local, they can be effectively explored using small, capped peptides, which act as minimal models for understanding folding patterns in larger peptides and proteins. Among the twenty naturally occurring amino acids, glycine (Gly) and proline (Pro) stand out due to their distinct conformational characteristics: glycine, which lacks a side chain, is the most flexible, whereas proline, featuring a cyclic imino group, is highly conformationally constrained. Importantly, the -Pro-Gly- sequence tends to favor a β-turn conformation, which is commonly found in the loop regions of β-hairpins.

In this presentation, I will discuss our detailed investigation of Pro-Gly containing capped PGX tripeptides (X = A, L, V, I) using a combination of FTIR spectroscopy, 2D-NMR, CD, gas-phase laser spectroscopy, single-crystal X-ray diffraction (XRD), and quantum chemical computations.1-5 Our study shows that PGA and PGL adopt a double β-turn structure across solid, solution, and gas phases, while PGV and PGI prefer an extended β-strand conformation in the solid and solution states but retain a double β-turn structure in the gas phase. These observations emphasize the subtle interplay between the inherent conformational tendencies of amino acid residues, sequence, and solvent effects in determining peptide folding motifs. Notably, the crystallization of these peptides in non-centrosymmetric space groups highlights their potential as functional materials with piezoelectric, ferroelectric, and nonlinear optical properties, thereby linking peptide structural chemistry with materials design.