Department of Biology, Tuskegee University, 1200 W Montgomery Rd, Tuskegee, AL 36088, USA.
Department of Mathematics and SimCenter, University of Tennessee at Chattanooga, 615 McCallie Ave, Chattanooga, TN 37403, USA.
J Theor Biol. 2021 Nov 21;529:110854. doi: 10.1016/j.jtbi.2021.110854. Epub 2021 Aug 3.
Protein folding, the process by which proteins attain a 3-dimensional conformation necessary for their function, remains an important unsolved problem in biology. A major gap in our understanding is how local properties of proteins relate to their global properties. In this manuscript, we use the Writhe and Torsion to introduce a new local topological/geometrical free energy that can be associated to 4 consecutive amino acids along the protein backbone. By analyzing a culled protein dataset from the PDB, our results show that high local topological free energy conformations are independent of sequence and may be involved in the rate limiting step in protein folding. By analyzing a set of 2-state single domain proteins, we find that the total local topological free energy of these proteins correlates with the experimentally observed folding rates reported in Plaxco et al. (2000).
蛋白质折叠是蛋白质获得其功能所需的三维构象的过程，仍然是生物学中一个重要的未解决问题。我们理解中的一个主要差距是蛋白质的局部性质如何与其整体性质相关。在本文中，我们使用挠率和扭转引入了一种新的局部拓扑/几何自由能，可以与沿蛋白质主链的 4 个连续氨基酸相关联。通过分析从 PDB 中筛选出的蛋白质数据集，我们的结果表明，高局部拓扑自由能构象与序列无关，可能与蛋白质折叠的限速步骤有关。通过分析一组 2 态单域蛋白质，我们发现这些蛋白质的总局部拓扑自由能与 Plaxco 等人报道的实验观察到的折叠速率相关。（2000 年）。
