Martin Osvaldo A, Vorobjev Yury, Scheraga Harold A, Vila Jorge A
Instituto de Matemática Aplicada San Luis, UNSL-CONICET, San Luis, Argentina.
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Science, Novosibirsk, Russia.
PeerJ Phys Chem. 2019 Oct 15;1. doi: 10.7717/peerj-pchem.2.
There is abundant theoretical evidence indicating that a mirror image of may occur during the protein folding process. However, as to whether such mirror image exists in solution is an unsolved issue. Here we provide outline of an experimental design aimed to detect the mirror image of in solution. The proposal is based on computational simulations indicating that the use of a mutant of protein A, namely Q10H, could be used to detect the mirror image conformation in solution. Our results indicate that the native conformation of the protein A should have a pKa, for the Q10H mutant, at ≈6.2, while the mirror-image conformation should have a pKa close to ≈7.3. Naturally, if all the population is in the native state for the Q10H mutant, the pKa should be ≈6.2, while, if all are in the mirror-image state, it would be ≈7.3, and, if it is a mixture, the pKa should be largerthan 6.2, presumably in proportion to the mirror population. In addition, evidence is provided indicating the tautomeric distribution of H10 must also change between the native and mirror conformations. Although this may not be completely relevant for the purpose of determining whether the protein A mirror image exists in solution, it could provide valuable information to validate the pKa findings. We hope this proposal will foster experimental work on this problem either by direct application of our proposed experimental design or serving as inspiration and motivation for other experiments.
有大量理论证据表明，在蛋白质折叠过程中可能会出现[具体物质]的镜像。然而，这种镜像在溶液中是否存在仍是一个未解决的问题。在此，我们提供了一个实验设计概要，旨在检测溶液中[具体物质]的镜像。该提议基于计算模拟，表明使用蛋白A的一个突变体，即Q10H，可用于检测溶液中的镜像构象。我们的结果表明，对于Q10H突变体，蛋白A的天然构象的pKa约为6.2，而镜像构象的pKa接近约7.3。自然地，如果Q10H突变体的所有群体都处于天然状态，pKa应为约6.2，而如果所有群体都处于镜像状态，pKa将为约7.3，如果是混合物，pKa应大于6.2，大概与镜像群体成比例。此外，有证据表明H10的互变异构分布在天然构象和镜像构象之间也必定会发生变化。尽管这对于确定蛋白A镜像是否存在于溶液中这一目的可能并非完全相关，但它可为验证pKa的发现提供有价值的信息。我们希望这个提议将通过直接应用我们提出的实验设计或为其他实验提供灵感和动力，促进关于这个问题的实验工作。
