School of Health Information Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
J Struct Biol. 2010 Apr;170(1):164-71. doi: 10.1016/j.jsb.2009.12.028. Epub 2010 Jan 7.
A structural characterization of multi-component cellular assemblies is essential to explain the mechanisms governing biological function. Macromolecular architectures may be revealed by integrating information collected from various biophysical sources - for instance, by interpreting low-resolution electron cryomicroscopy reconstructions in relation to the crystal structures of the constituent fragments. A simultaneous registration of multiple components is beneficial when building atomic models as it introduces additional spatial constraints to facilitate the native placement inside the map. The high-dimensional nature of such a search problem prevents the exhaustive exploration of all possible solutions. Here we introduce a novel method based on genetic algorithms, for the efficient exploration of the multi-body registration search space. The classic scheme of a genetic algorithm was enhanced with new genetic operations, tabu search and parallel computing strategies and validated on a benchmark of synthetic and experimental cryo-EM datasets. Even at a low level of detail, for example 35-40 A, the technique successfully registered multiple component biomolecules, measuring accuracies within one order of magnitude of the nominal resolutions of the maps. The algorithm was implemented using the Sculptor molecular modeling framework, which also provides a user-friendly graphical interface and enables an instantaneous, visual exploration of intermediate solutions.
对多组分细胞组装体进行结构特征分析对于解释控制生物功能的机制至关重要。通过整合来自各种生物物理源的信息，可以揭示大分子结构 - 例如，通过将低分辨率电子晶体显微镜重建与组成片段的晶体结构相关联来进行解释。在构建原子模型时，同时注册多个组件是有益的，因为它会引入额外的空间约束，以促进在地图内的天然位置。这种搜索问题的高维性质阻止了对所有可能解决方案的详尽探索。在这里，我们介绍了一种基于遗传算法的新方法，用于有效地探索多体配准搜索空间。经典的遗传算法方案通过新的遗传操作、禁忌搜索和并行计算策略得到了增强，并在合成和实验冷冻电镜数据集的基准上得到了验证。即使在低细节水平（例如 35-40 A）下，该技术也成功地注册了多个组分生物分子，测量精度在地图名义分辨率的一个数量级内。该算法是使用 Sculptor 分子建模框架实现的，该框架还提供了用户友好的图形界面，并能够即时、直观地探索中间解决方案。
