Linking Sequence to Disordered Protein Function

Intrinsically disordered proteins and protein regions (IDPs) are increasingly recognized as having specific, sequence-encoded functions despite lacking a stable three-dimensional structure. The lack of stable structure in IDPs offers unique and complementary functions, including binding promiscuity with high affinity, environmental sensitivity, and the ability to assemble into both structured and highly dynamic states. Yet our understanding of how the amino acid sequences of IDPs relate to their function is trailing far behind our understanding of the sequence-to-function link in well-folded proteins. Recently, numerous links between sequence and IDP function have emerged, buoyed by the development of state-of-the-art experimental and computational tools. Our vision for this meeting is to bring together scientists at all levels and from different fields to bridge the knowledge gap between IDP sequence and function. Establishing this link will help reveal the myriad roles IDPs play in biology and disease, increase our understanding of how the collective behavior of IDPs is encoded in sequence, and usher in a new era of functional disordered protein design.

Attendees are encouraged to present work aiming to:

• Understand the link between structure and function. Broadly defined, function includes (but is not limited to) biological activity, self-assembly, ligand or protein binding, specific material properties or structural dynamics.

• Develop experimental or computational methods to understand how changes to sequence alter functional properties in vitro and in the cell

• Explore the functional consequences of sequence variations

• Combine complementary experimental and computational methods to reveal links between sequence and function at low- and high-throughput

We encourage participation by scientists already working in the IDP field, biophysicists, polymer physicists, biochemists and cell biologists working on IDP-related molecular processes, scientists seeking to therapeutically target IDPs and others less familiar with the pervasive roles of IDPs in biology and disease for state-of-the-art insight. We especially encourage young scientists to attend this GRC and the accompanying GRS to learn about the scientific challenges and opportunities that await them.