Tunneling Group, Biotechnology Centre, Silesian University of Technology, ul. Krzywoustego 8, 44-100 Gliwice, Poland.
Biotechnology Centre, Silesian University of Technology, ul. Krzywoustego 8, 44-100 Gliwice, Poland.
Int J Mol Sci. 2020 Mar 26;21(7):2293. doi: 10.3390/ijms21072293.
Loops are the most variable and unorganized elements of the secondary structure of proteins. Their ability to shift their shape can play a role in the binding of small ligands, enzymatic catalysis, or protein-protein interactions. Due to the loop flexibility, the positions of their residues in solved structures show the largest B-factors, or in a worst-case scenario can be unknown. Based on the loops' movements' timeline, they can be divided into slow (static) and fast (flexible). Although most of the loops that are missing in experimental structures belong to the flexible loops group, the computational tools for loop reconstruction use a set of static loop conformations to predict the missing part of the structure and evaluate the model. We believe that these two loop types can adopt different conformations and that using scoring functions appropriate for static loops is not sufficient for flexible loops. We showed that common model evaluation methods, are insufficient in the case of flexible solvent-exposed loops. Instead, we recommend using the potential energy to evaluate such loop models. We provide a novel model selection method based on a set of geometrical parameters to distinguish between flexible and static loops without the use of molecular dynamics simulations. We have also pointed out the importance of water network and interactions with the solvent for the flexible loop modeling.
环是蛋白质二级结构中最具变异性和无组织性的元素。它们能够改变形状的能力在小分子配体的结合、酶催化或蛋白质-蛋白质相互作用中起着重要作用。由于环的灵活性，在已解决结构中，其残基的位置显示出最大的 B 因子，或者在最坏的情况下可能是未知的。根据环运动的时间线，可以将它们分为慢（静态）和快（灵活）两种类型。尽管实验结构中缺失的大多数环都属于灵活环组，但用于环重构的计算工具使用一组静态环构象来预测结构中缺失的部分，并评估模型。我们认为这两种环类型可以采用不同的构象，并且使用适用于静态环的评分函数对于灵活环来说是不够的。我们表明，常见的模型评估方法在灵活的溶剂暴露环的情况下是不够的。相反，我们建议使用势能来评估这种环模型。我们提供了一种新的基于一组几何参数的模型选择方法，用于在不使用分子动力学模拟的情况下区分灵活环和静态环。我们还指出了水网络和与溶剂相互作用对于灵活环建模的重要性。
