Residual dipolar couplings (RDCs) are unique probes of the structural and dynamical properties of biomolecules on the sub-millisecond time scale that can be used as restraints in ensemble molecular dynamics simulations to study the relationship between macromolecular motion and biological function. To date, however, this powerful strategy is applicable only to molecules that do not undergo shape changes on the time scale sampled by RDCs, thus preventing the study of key biological macromolecules such as multidomain and unstructured proteins. In this work, we circumvent this limitation by using an algorithm that explicitly computes the individual alignment tensors of the different ensemble members from their coordinates at each step in the simulation. As a first application, we determine an ensemble of conformations that accurately describes the structure and dynamics of chemically denatured ubiquitin. In analogy to dynamic refinement of folded, globular proteins, where simulations are initiated from average structures, we use statistical coil models as starting configuration because they represent the best available descriptions of unstructured proteins. We find that refinement with RDCs causes significant structural corrections and yields an ensemble that is in complete agreement with the measured RDCs and presents transient mid-range inter-residue interactions between strands beta(1) and beta(2) of the native protein, also observed in other studies based on trans-hydrogen bond (3)J(NC), scalar couplings and paramagnetic relaxation enhancements. Finally, and in spite of the high structural heterogeneity of the refined ensemble, we find that it can be cross-validated against RDCs not used to restrain the simulation. This method increases the range of systems that can be studied using ensemble simulations restrained by RDCs and is likely to yield new insights into how the large-scale motions of macromolecules relate to biological function.