biostudies-literatureDey SNational Institute of General Medical SciencesNIGMS NIH HHS6310-6323https://www.ebi.ac.uk/biostudies/studies/S-EPMC9561007biostudies-literatureUnknown18(10)For intrinsically disordered proteins (IDPs), a pressing question is how sequence codes for function. Dynamics serves as a crucial link, reminiscent of the role of structure in sequence-function relations of structured proteins. To define general rules governing sequence-dependent backbone dynamics, we carried out long molecular dynamics simulations of eight IDPs. Blocks of residues exhibiting large amplitudes in slow dynamics are rigidified by local inter-residue interactions or secondary structures. A long region or an entire IDP can be slowed down by long-range contacts or secondary-structure packing. On the other hand, glycines promote fast dynamics and either demarcate rigid blocks or facilitate multiple modes of local and long-range inter-residue interactions. The sequence-dependent backbone dynamics endows IDPs with versatile response to binding partners, with some blocks recalcitrant while others readily adapting to intermolecular interactions.Journal of chemical theory and computationSequence-Dependent Backbone Dynamics of Intrinsically Disordered Proteins.PMC9561007R35 GM118091Dey SMacAinsh MZhou HXfalseSequence-Dependent Backbone Dynamics of Intrinsically Disordered Proteins.For intrinsically disordered proteins (IDPs), a pressing question is how sequence codes for function. Dynamics serves as a crucial link, reminiscent of the role of structure in sequence-function relations of structured proteins. To define general rules governing sequence-dependent backbone dynamics, we carried out long molecular dynamics simulations of eight IDPs. Blocks of residues exhibiting large amplitudes in slow dynamics are rigidified by local inter-residue interactions or secondary structures. A long region or an entire IDP can be slowed down by long-range contacts or secondary-structure packing. On the other hand, glycines promote fast dynamics and either demarcate rigid blocks or facilitate multiple modes of local and long-range inter-residue interactions. The sequence-dependent backbone dynamics endows IDPs with versatile response to binding partners, with some blocks recalcitrant while others readily adapting to intermolecular interactions.2022-01-01T00:00:00Z2022 Oct2025-04-26T13:29:26.782Z2025-04-06T14:16:02.533ZS-EPMC95610073608434710.1021/acs.jctc.2c00328