Department of Computer Science, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Proc Natl Acad Sci U S A. 2023 Oct 31;120(44):e2301064120. doi: 10.1073/pnas.2301064120. Epub 2023 Oct 25.
Protein structure, both at the global and local level, dictates function. Proteins fold from chains of amino acids, forming secondary structures, α-helices and β-strands, that, at least for globular proteins, subsequently fold into a three-dimensional structure. Here, we show that a Ramachandran-type plot focusing on the two dihedral angles separated by the peptide bond, and entirely contained within an amino acid pair, defines a local structural unit. We further demonstrate the usefulness of this cross-peptide-bond Ramachandran plot by showing that it captures β-turn conformations in coil regions, that traditional Ramachandran plot outliers fall into occupied regions of our plot, and that thermophilic proteins prefer specific amino acid pair conformations. Further, we demonstrate experimentally that the effect of a point mutation on backbone conformation and protein stability depends on the amino acid pair context, i.e., the identity of the adjacent amino acid, in a manner predictable by our method.
蛋白质的结构，无论是在全局还是局部水平上，都决定了其功能。蛋白质由氨基酸链折叠形成二级结构，如α-螺旋和β-折叠，这些结构至少对于球状蛋白质来说，随后会折叠成三维结构。在这里，我们表明，一个集中在由肽键隔开的两个二面角上的 Ramachandran 型图，并且完全包含在一个氨基酸对中，定义了一个局部结构单元。我们进一步通过证明它捕获了卷曲区域中的β-转角构象，传统的 Ramachandran 型图异常值落入我们的图的占据区域，以及嗜热蛋白质偏好特定的氨基酸对构象，证明了这种跨肽键 Ramachandran 图的有用性。此外，我们通过实验证明，点突变对骨架构象和蛋白质稳定性的影响取决于氨基酸对的上下文，即相邻氨基酸的身份，这种影响可以通过我们的方法来预测。
