Institute of Theoretical and Experimental Biophysics, RAS, Institutskaya ul., 3, 142290 Pushchino, Moscow Oblast, Russia.
Molecules. 2024 Nov 15;29(22):5386. doi: 10.3390/molecules29225386.
Endolysins of bacteriophages, which degrade the bacterial cell wall peptidoglycan, are applicable in many industries to deal with biofilms and bacterial infections. While multi-domain endolysins have both enzymatically active and cell wall-binding domains, single-domain endolysins consist only of an enzymatically active domain, and their mechanism of peptidoglycan binding remains unexplored, for this is a challenging task experimentally. This research aimed to explore the binding mechanism of endolysins using computational approaches, namely molecular docking and bioinformatical tools, and analyze the performance of these approaches. The docking engine Autodock Vina 1.1.2 and the 3D-RISM module of AmberTools 24 were studied in the current work and used for receptor-ligand affinity and binding energy calculations, respectively. Two possible mechanisms of single-domain endolysin-ligand binding were predicted by Autodock Vina and verified by the 3D-RISM. As a result, the previously obtained experimental results on peptidoglycan binding of the isolated gamma phage endolysin PlyG enzymatically active domain were supported by molecular docking. Both methods predicted that single-domain endolysins are able to bind peptidoglycan, with Autodock Vina being able to give accurate numerical estimates of protein-ligand affinities and 3D-RISM providing comparative values.
噬菌体的内溶素可以降解细菌细胞壁的肽聚糖，在许多行业中都有应用，可以用来处理生物膜和细菌感染。多结构域内溶素既有酶活性结构域又有细胞壁结合结构域，而单结构域内溶素只含有酶活性结构域，其肽聚糖结合机制仍未被探索，因为这在实验上是一项具有挑战性的任务。本研究旨在使用计算方法（即分子对接和生物信息学工具）探索内溶素的结合机制，并分析这些方法的性能。在本研究中，使用 Autodock Vina 1.1.2 对接引擎和 AmberTools 24 的 3D-RISM 模块分别进行受体-配体亲和力和结合能计算。Autodock Vina 预测了单结构域内溶素-配体结合的两种可能机制，并通过 3D-RISM 进行了验证。结果，分子对接支持了先前关于分离的 gamma 噬菌体内溶素 PlyG 酶活性结构域对肽聚糖结合的实验结果。两种方法都预测了单结构域内溶素能够结合肽聚糖，Autodock Vina 能够准确地估计蛋白质-配体的亲和力，而 3D-RISM 则提供了比较值。
