‘Main Mechanical Forces-Chemical Interactions’ Interplay as a Tool to Elucidate Folding Mechanisms

Michele Larocca, Giuseppe Floresta, Daniele Verderese, Agostino Cilibrizzi

Research output: Contribution to journalArticlepeer-review


The folding of peptides and proteins is rigidly reliant on the ‘chemical information’ carried by the specific amino acid sequence. In this study, three polypeptides (PDBs: 2jof, 1res and 1prv) were investigated as model systems to assess their folded features, thereby enabling further understanding of mechanisms that play a role in regulating the folding process more widely. A novel physico-chemical approach of analysis is proposed herein, focusing on chemical interactions and their related mechanical forces that we trust are determinant to drive the folding. Through this methodology, we have predicted the conformations adopted by the three polypeptides and compared the outcomes to those experimentally determined, achieving a substantial structural agreement. Molecular dynamic simulations have been carried out to further support our calculations and structural results. Within the three models, we demonstrate that the interaction of each amino acid residue with its neighbour residues is a crucial determinant for the formation of the 3D stable native structures. This article provides initial evidence that the folding occurs by means of mechanical forces developed upon establishing chemical interactions amongst residues, which, in turn, are peculiar to each specific amino acid present in each position of the peptide chain.

Original languageEnglish
Article numbere24365
JournalPeptide Science
Early online date29 May 2024
Publication statusE-pub ahead of print - 29 May 2024
Externally publishedYes

Data Availability Statement

The data that support the findings of this study are available in the sup-plementary material of this article.


  • chemical interactions
  • dihedral angle calculations
  • folding mechanisms
  • main mechanical forces

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Biomaterials
  • Organic Chemistry

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