Assessing the binding properties of CASP14 targets and models.
Assessing the binding properties of CASP14 targets and models.
复制标题
作者：
Egbert M;Ghani U;Ashizawa R;Kotelnikov S;Nguyen T;Desta I;Hashemi N;Padhorny D;Kozakov D;Vajda S
一个重要的问题是，提交给CASP的模型在多大程度上保留了目标结构的属性。我们研究了与绑定相关的几个性质。首先，我们探索作为探针的小分子的结合，并计算每个残基与此类探针之间的相互作用次数，产生结合指纹。通过计算两个指纹的相关系数来确定两个指纹之间的相似性，一个指纹用于X射线结构，另一个用于模型。指纹相似度与整体精确度的相关性很弱，GDT_TS大于80是表面结合性质保持的必要条件，但不是充分条件。这种方法的优点是，它可以在没有关于潜在配体及其结合位点的信息的情况下进行。后一种信息对于一些靶标是可用的，我们探索了CASP14模型是否可以用于预测结合位点和对接小配体。最后，我们通过将X射线结构和模型对接到它们在络合物中的相互作用伙伴来测试模型再现蛋白质-蛋白质相互作用的能力。分析表明，在CASP14中，单个结构域模型的质量接近X射线结晶学提供的质量，因此这些模型可以成功地用于识别结合和调控位点，以及组装必需的蛋白质-蛋白质复合体。然而，配体对接的成功往往取决于结合界面的精细细节，因此可能需要通过模拟方法来考虑构象变化。
An important question is how well the models submitted to CASP retain the properties of target structures. We investigate several properties related to binding. First we explore the binding of small molecules as probes, and count the number of interactions between each residue and such probes, resulting in a binding fingerprint. The similarity between two fingerprints, one for the X-ray structure and the other for a model, is determined by calculating their correlation coefficient. The fingerprint similarity weakly correlates with global measures of accuracy, and GDT_TS higher than 80 is a necessary but not sufficient condition for the conservation of surface binding properties. The advantage of this approach is that it can be carried out without information on potential ligands and their binding sites. The latter information was available for a few targets, and we explored whether the CASP14 models can be used to predict binding sites and to dock small ligands. Finally, we tested the ability of models to reproduce protein–protein interactions by docking both the X-ray structures and the models to their interaction partners in complexes. The analysis showed that in CASP14 the quality of individual domain models is approaching that offered by X-ray crystallography, and hence such models can be successfully used for the identification of binding and regulatory sites, as well as for assembling obligatory protein–protein complexes. Success of ligand docking, however, often depends on fine details of the binding interface, and thus may require accounting for conformational changes by simulation methods.
登录
查看更多内容
影响因子：
6
作者：
Egbert M;Porter KA;Ghani U;Kotelnikov S;Nguyen T;Ashizawa R;Kozakov D;Vajda S
通讯作者：
Vajda S
影响因子：
3
作者：
Bordogna, Annalisa;Pandini, Alessandro;Bonati, Laura
通讯作者：
Bonati, Laura
影响因子：
14.8
作者：
Kozakov D;Hall DR;Xia B;Porter KA;Padhorny D;Yueh C;Beglov D;Vajda S
通讯作者：
Vajda S
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
7.4
作者：
Hillisch A;Pineda LF;Hilgenfeld R
通讯作者：
Hilgenfeld R