REWIRE: Reading, Writing, and Interpreting the Rules of IDP Evolution  

Proteins carry out most functions in the cell and are widely used to address societal challenges, including as drugs, industrial enzymes, and components of food. A central dogma in protein science is that a protein’s function is determined by its three-dimensional structure. Over the past 20 years, however, it has become clear that so-called intrinsically disordered proteins defy this structure–function relationship: they are highly dynamic molecules without a well-defined shape, yet they play key biological roles and are pervasive across all kingdoms of life.

In REWIRE, we will learn the rules for reading and writing amino acid sequences of intrinsically disordered proteins. To do so, we will combine molecular simulations, machine learning, biophysics, and cell biology to discover the language that encodes the function and evolution of disordered proteins. This will transform our ability to predict and design the functions of disordered proteins and to unravel hidden fundamental principles with key roles in disease.