Raymond and Beverly Sackler Faculty of Exact Sciences, Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel.
Proteins. 2010 Nov 15;78(15):3205-11. doi: 10.1002/prot.22845.
Structural models of macromolecular assemblies are instrumental for gaining a mechanistic understanding of cellular processes. Determining these structures is a major challenge for experimental techniques, such as X-ray crystallography, NMR spectroscopy and electron microscopy (EM). Thus, computational modeling techniques, including molecular docking, are required. The development of most molecular docking methods has so far been focused on modeling of binary complexes. We have recently introduced the MultiFit method for modeling the structure of a multisubunit complex by simultaneously optimizing the fit of the model into an EM density map of the entire complex and the shape complementarity between interacting subunits. Here, we report algorithmic advances of the MultiFit method that result in an efficient and accurate assembly of the input subunits into their density map. The successful predictions and the increasing number of complexes being characterized by EM suggests that the CAPRI challenge could be extended to include docking-based modeling of macromolecular assemblies guided by EM.
大分子组装体的结构模型对于理解细胞过程的机制至关重要。确定这些结构是 X 射线晶体学、NMR 光谱学和电子显微镜（EM）等实验技术的主要挑战。因此，需要计算建模技术，包括分子对接。到目前为止，大多数分子对接方法的开发都集中在二元复合物的建模上。我们最近引入了 MultiFit 方法，通过同时优化模型与整个复合物的 EM 密度图的拟合以及相互作用亚基之间的形状互补性，来模拟多亚基复合物的结构。在这里，我们报告了 MultiFit 方法的算法进展，这些进展可有效且准确地将输入亚基组装到其密度图中。成功的预测以及越来越多的复合物通过 EM 进行特征描述表明，CAPRI 挑战可以扩展到包括由 EM 指导的基于对接的大分子组装体建模。
