TY - JOUR TI - Modelling dynamics in protein crystal structures by ensemble refinement AU - Burnley, B Tom AU - Afonine, Pavel V AU - Adams, Paul D AU - Gros, Piet A2 - Brunger, Axel T VL - 1 PY - 2012 DA - 2012/12/18 SP - e00311 C1 - eLife 2012;1:e00311 DO - 10.7554/eLife.00311 UR - https://doi.org/10.7554/eLife.00311 AB - Single-structure models derived from X-ray data do not adequately account for the inherent, functionally important dynamics of protein molecules. We generated ensembles of structures by time-averaged refinement, where local molecular vibrations were sampled by molecular-dynamics (MD) simulation whilst global disorder was partitioned into an underlying overall translation–libration–screw (TLS) model. Modeling of 20 protein datasets at 1.1–3.1 Å resolution reduced cross-validated Rfree values by 0.3–4.9%, indicating that ensemble models fit the X-ray data better than single structures. The ensembles revealed that, while most proteins display a well-ordered core, some proteins exhibit a ‘molten core’ likely supporting functionally important dynamics in ligand binding, enzyme activity and protomer assembly. Order–disorder changes in HIV protease indicate a mechanism of entropy compensation for ordering the catalytic residues upon ligand binding by disordering specific core residues. Thus, ensemble refinement extracts dynamical details from the X-ray data that allow a more comprehensive understanding of structure–dynamics–function relationships. KW - protein KW - crystallography KW - structure KW - function KW - dynamics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -