The discovery of intrinsically disordered proteins and regions (IDPRs) challenges our understanding of the physical chemistry of biological mechanisms. IDPRs increase the reach of biomolecular systems to project far and engage in multiple interactions, moving efficiently over nanometer distances. Yet, we still miss methods to investigate the geometry and timescales of these nanometer motions with high resolution. We will develop an integrative experimental and computational framework to characterize nanometer motions in IDPRs at atomic resolution, exploiting synergies between paramagnetic NMR, electron paramagnetic resonance (EPR) and molecular dynamics (MD) simulations. A series of methodological innovations will be pursued in each of these fields: (1) we will tackle a key limitation that currently prohibits the quantitative interpretation of NMR relaxation effects due to the interaction with electrons by quantifying them over a broad range of the most relevant magnetic fields with a unique sample shuttle apparatus combined with high magnetic fields. (2) We will reduce the current flaws in molecular dynamics force fields for IDPs by direct improvement of the force fields and selection of MD trajectories based on experimental constraints with a new protocol. (3) The complementary information provided by paramagnetic NMR and EPR will allow us to carry an original quantitative analysis with MD simulations leading to an unprecedented description of the kinetics and conformational pathways of nanometer motions in IDPs with atomic resolution. This methodology will be developed on the IDPRs from key proteins in the non-homologous end joining (NHEJ) pathway, a process essential for the repair of DNA double-strand breaks and adaptive immunity: the long disordered region of the enzyme Artemis and the IDPRs of the scaffolding and regulation proteins XLF and XRCC4. The consortium brings together specialists in NMR methodology and instrumentation, IDP NMR, molecular dynamics simulations, protein EPR, and the biology of NHEJ. The NANO-DISPRO project will provide new tools to investigate the kinetic and thermodynamic principles that underlie the function of IDPRs.