Mirela Bota Patricia, Hernandez Altair C, Segura Joan, Gallego Oriol, Oliva Baldo, Fernandez-Fuentes Narcis
Structural Bioinformatics Lab (GRIB-IMIM), Universitat Pompeu Fabra, 08950 Barcelona, Catalonia, Spain. Electronic address: https://twitter.com/PatriciaMBota.
Live-cell Structural Biology, Department of Medicine and Life Sciences, University Pompeu Fabra, Barcelona 08005, Catalonia, Spain. Electronic address: https://twitter.com/pantair.
J Mol Biol. 2023 Jul 15;435(14):168055. doi: 10.1016/j.jmb.2023.168055. Epub 2023 Mar 21.
The human interactome is composed of around half a million interactions according to recent estimations and it is only for a small fraction of those that three-dimensional structural information is available. Indeed, the structural coverage of the human interactome is very low and given the complexity and time-consuming requirements of solving protein structures this problem will remain for the foreseeable future. Structural models, or predictions, of protein complexes can provide valuable information when the experimentally determined 3D structures are not available. Here we present CM2D3, a relational database containing structural models of the whole human interactome derived both from comparative modeling and data-driven docking. Starting from a consensus interactome derived from integrating several interactomics databases, a strategy was devised to derive structural models by computational means. Currently, CM2D3 includes 33338 structural models of which 5121 derived from comparative modeling and the remaining from docking. Of the latter, the structures of 14554 complexes were derived from monomers modeled by M4T while the rest were modeled with structures as predicted by AlphaFold2. Lastly, CM2D3 complements existing resources by focusing on models derived from both free-docking, as opposed to template-based docking, and hence expanding the available structural information on protein complexes to the scientific community. Database URL:http://www.bioinsilico.org/CM2D3.
根据最近的估计，人类相互作用组由大约50万种相互作用组成，而其中只有一小部分有三维结构信息。实际上，人类相互作用组的结构覆盖率非常低，并且鉴于解析蛋白质结构的复杂性和耗时性，在可预见的未来这个问题仍将存在。当无法获得实验确定的三维结构时，蛋白质复合物的结构模型或预测可以提供有价值的信息。在此，我们展示了CM2D3，这是一个关系数据库，包含通过比较建模和数据驱动对接得到的整个人类相互作用组的结构模型。从整合多个相互作用组学数据库得到的共识相互作用组出发，设计了一种通过计算手段推导结构模型的策略。目前，CM2D3包含33338个结构模型，其中5121个来自比较建模，其余来自对接。在后者中，14554个复合物的结构是由M4T建模的单体推导而来，其余则是用AlphaFold2预测的结构建模。最后，CM2D3专注于源自自由对接而非基于模板对接的模型，从而补充了现有资源，进而向科学界扩展了关于蛋白质复合物的可用结构信息。数据库网址：http://www.bioinsilico.org/CM2D3
