Dihedral Angle Calculations To Elucidate the Folding of Peptides through Its Main Mechanical Forces.

This study reports a general method to calculate dihedral angles (φ and ψ) of a given amino acid sequence, focusing on potential energy and torque moment concepts. By defining these physical measures in relation to the chemical interactions that occur on each single amino acid residue within a peptide, we analyze the folding process as the result of main mechanical forces (MMFs) exerted in the specific amino acid chain of interest. As a proof of concept, Leu-enkephalin was initially used as a model peptide to carry out the theoretical study. Our data show agreement between calculated Leu-enkephalin backbone dihedral angles and the corresponding experimentally determined X-ray values. Hence, we used calcitonin to validate our MMF-based method on a larger peptide, i.e., 32 amino acid residues forming an α-helix. Through a similar approach (although simplified with regard to electrostatic interactions), the calculations for calcitonin also demonstrate a good agreement with experimental values. This study offers new opportunities to analyze peptides' amino acid sequences and to help in the prediction of how they must fold, assisting in the development of new computational techniques in the field.