Department of Computer Science, Old Dominion University, Norfolk, VA 23529, USA.
Molecules. 2021 Nov 22;26(22):7049. doi: 10.3390/molecules26227049.
Although atomic structures have been determined directly from cryo-EM density maps with high resolutions, current structure determination methods for medium resolution (5 to 10 Å) cryo-EM maps are limited by the availability of structure templates. Secondary structure traces are lines detected from a cryo-EM density map for α-helices and β-strands of a protein. A topology of secondary structures defines the mapping between a set of sequence segments and a set of traces of secondary structures in three-dimensional space. In order to enhance accuracy in ranking secondary structure topologies, we explored a method that combines three sources of information: a set of sequence segments in 1D, a set of amino acid contact pairs in 2D, and a set of traces in 3D at the secondary structure level. A test of fourteen cases shows that the accuracy of predicted secondary structures is critical for deriving topologies. The use of significant long-range contact pairs is most effective at enriching the rank of the maximum-match topology for proteins with a large number of secondary structures, if the secondary structure prediction is fairly accurate. It was observed that the enrichment depends on the quality of initial topology candidates in this approach. We provide detailed analysis in various cases to show the potential and challenge when combining three sources of information.
虽然已经可以直接从具有高分辨率的冷冻电镜密度图中确定原子结构，但目前用于中等分辨率（5 至 10 Å）冷冻电镜图的结构确定方法受到结构模板可用性的限制。二级结构轨迹是从蛋白质的α-螺旋和β-折叠的冷冻电镜密度图中检测到的线。二级结构的拓扑结构定义了在三维空间中一组序列片段和一组二级结构轨迹之间的映射关系。为了提高对二级结构拓扑结构排序的准确性，我们探索了一种结合三种信息源的方法：一维的一组序列片段、二维的一组氨基酸接触对和三维的二级结构水平的一组轨迹。对十四个案例的测试表明，预测二级结构的准确性对于推导拓扑结构至关重要。如果二级结构预测相当准确，那么使用重要的长程接触对对于富含具有大量二级结构的蛋白质的最大匹配拓扑结构的排名是最有效的。观察到这种富集取决于该方法中初始拓扑候选的质量。我们在各种情况下提供了详细的分析，以展示结合三种信息源的潜力和挑战。
