Department of Bioinformatics and Life Science, Soongsil University, Seoul 06978, Korea.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia.
Molecules. 2022 Jul 30;27(15):4887. doi: 10.3390/molecules27154887.
Quorum sensing (QS) is a bacterial communication using signal molecules, by which they sense population density of their own species, leading to group behavior such as biofilm formation and virulence. Autoinducer-2 (AI2) is a QS signal molecule universally used by both gram-positive and gram-negative bacteria. Inhibition of QS mediated by AI2 is important for various practical applications, including prevention of gum-disease caused by biofilm formation of oral bacteria. In this research, molecular docking and molecular dynamics (MD) simulations were performed for molecules that are chemically similar to known AI2 inhibitors that might have a potential to be quorum sensing inhibitors. The molecules that form stable complexes with the AI2 receptor protein were found, suggesting that they could be developed as a novel AI2 inhibitors after further in vitro validation. The result suggests that combination of ligand-based drug design and computational methods such as MD simulation, and experimental verification, may lead to development of novel AI inhibitor, with a broad range of practical applications.
群体感应（QS）是一种细菌使用信号分子进行的通讯方式，通过这种方式，它们可以感知自身物种的种群密度，从而导致群体行为，如生物膜形成和毒力。自诱导物-2（AI2）是一种QS 信号分子，普遍存在于革兰氏阳性菌和革兰氏阴性菌中。通过 AI2 抑制 QS 对于各种实际应用非常重要，包括预防由口腔细菌生物膜形成引起的牙龈疾病。在这项研究中，对与已知 AI2 抑制剂具有化学相似性的分子进行了分子对接和分子动力学（MD）模拟，这些分子可能具有成为群体感应抑制剂的潜力。发现了与 AI2 受体蛋白形成稳定复合物的分子，这表明它们可能在进一步的体外验证后被开发为新型 AI2 抑制剂。结果表明，结合基于配体的药物设计和计算方法（如 MD 模拟）以及实验验证，可能会开发出具有广泛实际应用的新型 AI 抑制剂。
