Biological Insights from Integrative Modeling of Intrinsically Disordered Protein Systems

TL;DR

This review discusses how integrative modeling approaches are used to understand the structure, dynamics, and functions of intrinsically disordered proteins, highlighting recent biological insights and methodological challenges.

Contribution

It provides a comprehensive overview of integrative modeling techniques applied to disordered proteins and summarizes key biological findings from these approaches.

Findings

Structural characterization of disordered regions involved in binding and phase separation

Insights into drug targeting of disordered regions

Integration of diverse experimental and computational data enhances understanding

Abstract

Intrinsically disordered proteins and regions are increasingly appreciated for their abundance in the proteome and the many functional roles they play in the cell. In this short review, we describe a variety of approaches used to obtain biological insight from the structural ensembles of disordered proteins, regions, and complexes and the integrative biology challenges that arise from combining diverse experiments and computational models. Importantly, we highlight findings regarding structural and dynamic characterization of disordered regions involved in binding and phase separation, as well as drug targeting of disordered regions, using a broad framework of integrative modeling approaches.