Department of Chemistry, Federal University of Paraíba, Cidade Universitária, Joao Pessoa, PB, 58051-900, Brazil.
Department of Biotechnology, Federal University of Paraíba, Cidade Universitária, Joao Pessoa, PB, 58051-900, Brazil.
J Mol Model. 2022 Mar 31;28(4):108. doi: 10.1007/s00894-022-05094-y.
The role of knots in proteins remains elusive. Some studies suggest an impact on stability; the difficulty in comparing systems to assess this effect, however, has been a significant challenge. In this study, we produced and analyzed molecular dynamic trajectories considering three different temperatures of two variants of ornithine transcarbamylase (OTC), only one of which has a 3 knot, in order to evaluate the relative stability of the two molecules. RMSD showed equilibrated structures for the produced trajectories, and RMSF showed subtle differences in flexibility. In the knot moiety, the knotted protein did not show a great deal of fluctuation at any temperature. For the unknotted protein, the residue GLY243 showed a high fluctuation in the corresponding moiety. The fraction of native contacts (Q) showed a similar profile at all temperatures, with the greatest decrease by 436 K. The investigation of conformational behavior with principal component analysis (PCA) and dynamic cross-correlation map (DCCM) showed that knotted protein is less likely to undergo changes in its conformation under the conditions employed compared to unknotted. PCA data showed that the unknotted protein had greater dispersion in its conformations, which suggests that it has a greater capacity for conformation transitions in response to thermal changes. DCCM graphs comparing the 310 K and 436 K temperatures showed that the knotted protein had less change in its correlation and anti-correlation movements, indicating stability compared to the unknotted.
蛋白质中结的作用仍然难以捉摸。一些研究表明它对稳定性有影响；然而，难以将系统进行比较以评估这种影响一直是一个重大挑战。在这项研究中，我们产生并分析了考虑两种鸟氨酸转氨甲酰酶（OTC）变体的三个不同温度的分子动力学轨迹，其中只有一种变体有 3 个结，以评估这两个分子的相对稳定性。RMSD 显示产生的轨迹达到了平衡结构，RMSF 显示出柔韧性的细微差异。在结部分，打结蛋白在任何温度下都没有很大的波动。对于无结蛋白，残基 GLY243 在相应的部分显示出很高的波动。天然接触分数（Q）在所有温度下显示出相似的曲线，在 436 K 时下降最大。用主成分分析（PCA）和动态互相关图（DCCM）对构象行为的研究表明，与无结蛋白相比，打结蛋白在实验条件下不太可能发生构象变化。PCA 数据表明，无结蛋白的构象分散度更大，这表明它在响应热变化时具有更大的构象转变能力。比较 310 K 和 436 K 温度的 DCCM 图表明，与无结蛋白相比，打结蛋白的相关性和反相关性运动变化较小，表明其稳定性更高。
