Department of Chemistry and Biochemistry, Old Dominion University, Norfolk, VA, 23529, USA.
Department of Computer Science, Old Dominion University, Norfolk, VA, 23529, USA.
Protein J. 2019 Oct;38(5):497-505. doi: 10.1007/s10930-019-09850-7.
Understanding and computationally predicting the protein folding process remains one of the most challenging scientific problems and has uniquely garnered the interdisciplinary efforts of researchers from both the biological, chemical, physical and computational disciplines. Previous studies have demonstrated the importance of long-range interactions in guiding the native structure. However, predicting how the native long-range interaction network forms to generate a specific topology from among all other conformations remains unresolved. The present research study conducts an exploratory study to identify amino acids and long-range interactions that have the potential to play a key role in building and maintaining the protein topology. Towards this end, the application of network science is utilized and developed to analyze the structures of a group of proteins that share a common Greek-key topology but differ in sequence, secondary structure and function. We investigate the idea that the residues with high betweeness centrality score are potentially significant in maintaining the protein network and in governing the Greek-key topology. This hypothesis is tested by two different computational methods: through a fragmentation test and by the analysis of diameter impacts. In summary, we find a subset of selected residues in similar geographical positions in all model proteins, which demonstrates the role of these specific residues and regions in governing the Greek-key topology from a network perspective.
理解和计算预测蛋白质折叠过程仍然是最具挑战性的科学问题之一，它独特地吸引了来自生物学、化学、物理和计算等多个学科的研究人员的跨学科努力。以前的研究已经证明了长程相互作用在指导天然结构中的重要性。然而，预测天然长程相互作用网络如何形成，以从所有其他构象中产生特定的拓扑结构，仍然没有得到解决。本研究进行了一项探索性研究，以确定在构建和维持蛋白质拓扑结构中可能发挥关键作用的氨基酸和长程相互作用。为此，应用网络科学进行分析，以研究一组具有共同希腊钥匙拓扑结构但在序列、二级结构和功能上不同的蛋白质的结构。我们研究了具有高介数中心度得分的残基在维持蛋白质网络和控制希腊钥匙拓扑结构方面可能具有重要意义的想法。通过两种不同的计算方法来检验这一假设：通过碎片测试和直径影响分析。总之，我们在所有模型蛋白质中都找到了一组位于相似地理位置的选定残基，这从网络角度证明了这些特定残基和区域在控制希腊钥匙拓扑结构中的作用。
