Centre de Biochimie Structurale (CBS), INSERM, CNRS and Université de Montpellier, 29, rue de Navacelles, 34090 Montpellier, France.
Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Structure. 2021 Sep 2;29(9):1074-1090.e4. doi: 10.1016/j.str.2021.03.017. Epub 2021 Apr 15.
Transient biomolecular interactions play crucial roles in many cellular signaling and regulation processes. However, deciphering the structure of these assemblies is challenging owing to the difficulties in isolating complexes from the individual partners. The additive nature of small-angle X-ray scattering (SAXS) data allows for probing the species present in these mixtures, but decomposition into structural and thermodynamic information is difficult. We present a chemometric approach enabling the decomposition of titration SAXS data into species-specific information. Using extensive synthetic SAXS data, we demonstrate that robust decomposition can be achieved for titrations with a maximum fraction of complex of 0.5 that can be extended to 0.3 when two orthogonal titrations are simultaneously analyzed. The effect of the structural features, titration points, relative concentrations, and noise are thoroughly analyzed. The validation of the strategy with experimental data highlights the power of the approach to provide unique insights into this family of biomolecular assemblies.
瞬态生物分子相互作用在许多细胞信号转导和调控过程中起着至关重要的作用。然而，由于从单个伴侣中分离复合物的困难，这些组装体的结构解析具有挑战性。小角 X 射线散射（SAXS）数据的加和性质允许探测这些混合物中存在的物种，但将其分解为结构和热力学信息是困难的。我们提出了一种化学计量学方法，能够将滴定 SAXS 数据分解为具有特定物种的信息。使用广泛的合成 SAXS 数据，我们证明对于最大复合物分数为 0.5 的滴定，可以实现稳健的分解，当同时分析两个正交滴定时，可以扩展到 0.3。彻底分析了结构特征、滴定点、相对浓度和噪声的影响。用实验数据验证该策略突出了该方法的强大功能，可提供对这组生物分子组装体的独特见解。
