Into the Unknown: From Structure to Disorder in Protein Function Prediction
Journal:
arXiv
Published Date:
Jun 6, 2025
Abstract
Intrinsically disordered regions (IDRs) account for one-third of the human
proteome and play essential biological roles. However, predicting the functions
of IDRs remains a major challenge due to their lack of stable structures, rapid
sequence evolution, and context-dependent behavior. Many predictors of protein
function neglect or underperform on IDRs. Recent advances in computational
biology and machine learning, including protein language models, alignment-free
approaches, and IDR-specific methods, have revealed conserved bulk features and
local motifs within IDRs that are linked to function. This review highlights
emerging computational methods that map the sequence-function relationship in
IDRs, outlines critical challenges in IDR function annotation, and proposes a
community-driven framework to accelerate interpretable functional predictions
for IDRs.
