Study of the three-dimensional structure of tryptophan zipper peptides through ¹H NMR chemical shifts calculations

Abstract

Abstract Most biological functions of proteins are directly connected to their primary structures and, encoded by these, to the spatial conformations they assume in solution. Therefore, the study of the three-dimensional structures of proteins is essential for the complete understanding of their functions. Nowadays, several methods are commonly used for the structural determination of proteins, such as Nuclear Magnetic Resonance (NMR) spectroscopy and X-ray Crystallography. However, these methodologies have limitations, which can make the structural study of proteins an arduous and costly process. In this scenario, quantum-mechanical calculations of chemical shifts are a potential tool to support experimental techniques. In this work, we intend to investigate the applicability of NMR chemical shift calculations in the study of three-dimensional structures of peptides. For this, we selected the peptide Tryptophan Zipper 1 (Trpzip 1) as a study model. In addition, in order to analyze the stability of the three-dimensional structure elements of tryptophan zippers against changes in the sequence, a peptide with a mutation in the primary structure of Trpzip 1 was proposed. Through chemical shifts calculations, it was possible to identify a probable structural change in the β-turn region of the mutant peptide against Trpzip 1.