EPJ Web of Conferences 366, 01007 (2026)
https://doi.org/10.1051/epjconf/202636601007

Protein order and disorder: A quantitative in silico analysis

Université Paris Cité and Université de la Réunion, INSERM, EFS, BIGR U1134, DSIMB Bioinformatics team, 75015 Paris, France

^* Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.

Published online: 29 April 2026

Abstract

Proteins are fundamental biological macromolecules responsible for a wide range of cellular functions. Traditionally, a central paradigm linked the amino acid sequence to a unique, ordered three-dimensional structure that underlies biological activity. While it has long been recognized that proteins are not rigid and contain flexible regions necessary for function, it was only in the late 1990s that attention turned to intrinsically disordered regions (IDRs) and intrinsically disordered proteins (IDPs)—segments or entire proteins that lack stable tertiary structures and exist as dynamic ensembles. To analyse local conformations in structured proteins, we developed a structural alphabet, known as Protein Blocks (PBs). This tool enables a residue-level description of backbone geometry and has proven effective in applications such as structure prediction and the analysis of molecular dynamics simulations. Building on this framework, PB analysis was extended to disordered proteins and introduced an entropy-based gradient that characterizes regions along a continuum from rigid to fully disordered. This scale represents the first model to provide a unified description of structural dynamics, bridging the gap between ordered and disordered states. It has been successfully applied in various studies, offering new insights into the complex conformational behaviour of proteins.