Local interactions and transient secondary structures govern backbone dynamics of intrinsically disordered proteins

The lack of well-defined structures in intrinsically disordered proteins (IDPs) calls for a fundamental reassessment of how their amino-acid sequences code for functions. Some attention has been paid to nascent structures, but a missing link is sequence-dependent backbone dynamics, which we previously showed to arise from the formation of correlated segments stabilized by polyproline II (PPII) helices and salt bridges in the ChiZ disordered N-terminal region.¹ To define general rules governing sequence-dependent backbone dynamics, we performed molecular dynamics simulations on eight IDPs. Nearly all above-average transverse relaxation rates and heteronuclear Overhauser enhancements along the sequence were attributable to interactions between side chains and formation of secondary structures. PPII stretches are the most common form of transient secondary structures, and are found in most IDPs and are often stabilized by local interactions. However, in some IDPs, stable α-helices are also present. These locally rigidified elements may code for nascent structures, whereas segments with fast dynamics may readily adapt to binding partners.²

1. Hicks, A. et al. Biomolecules 10, 946 (2020).

2. Hicks, A. et al. JACS Au 1, 66-78 (2021).