Data from: Modelling dynamics in protein crystal structures by ensemble refinement

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 R_free 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.

基于X射线数据构建的单结构模型，无法充分反映蛋白质分子固有的、且对功能至关重要的动态特性。本研究通过时间平均精修（time-averaged refinement）方法构建了结构集合：其中局部分子振动通过分子动力学（MD）模拟进行采样，而整体无序性则被拆解为基础的整体平动-转动-螺旋（translation-libration-screw, TLS）模型。对分辨率介于1.1~3.1埃的20组蛋白质数据集进行建模后，经交叉验证的自由R因子（R_free）值降低了0.3%~4.9%，这表明结构集合模型相较于单结构模型更适配X射线数据。该结构集合揭示：尽管多数蛋白质的核心区域排布规整，但部分蛋白质呈现出‘熔态核心’，这一结构很可能支撑配体结合、酶活性与原聚体组装等对功能至关重要的动态过程。HIV蛋白酶的有序-无序变化表明，其通过使特定核心残基发生无序化，来补偿配体结合时催化残基有序化所需的熵变。由此可见，时间平均精修可从X射线数据中提取动态细节，从而帮助研究者更全面地理解结构-动态-功能之间的关联。