Department of Chemistry, Federal University of Paraíba, Cid. Universitária, João Pessoa, 58051-900, Paraíba, Brazil.
Department of Chemistry, Federal University of Pernambuco, Cid. Universitária, Recife, 50670-901, Pernambuco, Brazil.
J Mol Model. 2024 Jul 15;30(8):265. doi: 10.1007/s00894-024-06009-9.
Geometrical knots are rare structural arrangements in proteins in which the polypeptide chain ties itself into a knot, which is very intriguing due to the uncertainty of their impact on the protein properties. Presently, classical molecular dynamics is the most employed technique in the few studies found on this topic, so any information on how the presence of knots affects the reactivity and electronic properties of proteins is even scarcer. Using the electronic structure methods and quantum chemical descriptors analysis, we found that the same amino-acid residues in the knot core have statistically larger values for the unknotted protein, for both hard-hard and soft-soft interaction descriptors. In addition, we present a computationally feasible protocol, where we show it is possible to separate the contribution of the geometrical knot to the reactivity and other electronic structure properties.
In order to investigate these systems, we used PRIMoRDiA, a new software developed by our research group, to explore the electronic structure of biological macromolecules. We evaluated several local quantum chemical descriptors to unveil relevant patterns potentially originating from the presence of the geometrical knot in two proteins, belonging to the ornithine transcarbamylase family. We compared several sampled structures from these two enzymes that are highly similar in both tertiary structure and function, but one of them has a knot whereas the other does not. The sampling was carried out through molecular dynamics simulations using ff14SB force field along 50 ns, and the semiempirical convergence was performed with PM7 Hamiltonian.
几何结是蛋白质中罕见的结构排列，其中多肽链自身打结，由于其对蛋白质性质的影响不确定，因此非常有趣。目前，在为数不多的关于这个主题的研究中，经典分子动力学是最常用的技术，因此关于结的存在如何影响蛋白质的反应性和电子性质的信息甚至更少。使用电子结构方法和量子化学描述符分析，我们发现对于硬-硬和软-软相互作用描述符，结核中的相同氨基酸残基在无结蛋白中具有统计学上更大的值。此外，我们提出了一种计算上可行的方案，其中我们展示了分离几何结对反应性和其他电子结构性质的贡献是可能的。
为了研究这些系统，我们使用了由我们的研究小组开发的新软件 PRIMoRDiA 来探索生物大分子的电子结构。我们评估了几个局部量子化学描述符，以揭示可能源自两种鸟氨酸转氨甲酰酶家族蛋白质中几何结存在的相关模式。我们比较了这两种酶的几个结构样本，它们在三级结构和功能上非常相似，但其中一种有结，而另一种没有。采样是通过使用 ff14SB 力场进行分子动力学模拟 50ns 来进行的，半经验收敛是用 PM7 哈密顿量进行的。
