Group of Investigation in Oral Health, Faculty of Dentistry, Antonio Nariño University, Av. Bolívar # 49 North-30, Armenia 630001, Quindío, Colombia.
GYMOL Group, Faculty of Health Sciences, Quindío University, Street 12N, Armenia 630001, Quindío, Colombia.
Int J Mol Sci. 2020 Dec 31;22(1):377. doi: 10.3390/ijms22010377.
is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II (Ag I/II) of is among the most important adhesins in this process, and is involved in the adhesion to the tooth surface and the bacterial co-aggregation in the early stage of biofilm formation. However, this protein has not been used as a target in a virtual strategy search for inhibitors. Based on the predicted binding affinities, drug-like properties and toxicity, molecules were selected and evaluated for their ability to reduce adhesion. A virtual screening of 883,551 molecules was conducted; cytotoxicity analysis on fibroblast cells, adhesion studies, scanning electron microscopy analysis for bacterial integrity and molecular dynamics simulation were also performed. We found three molecules ZINC19835187 (ZI-187), ZINC19924939 (ZI-939) and ZINC19924906 (ZI-906) without cytotoxic activity, which inhibited about 90% the adhesion of to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides new molecules that targets Ag I/II and have the capacity to inhibit in vitro the adhesion on polystyrene microplates.
是主要的早期定植致龋细菌，因为它能识别唾液膜受体。在这个过程中， 的抗原 I/II（Ag I/II）是最重要的黏附素之一，它参与了细菌在生物膜形成的早期阶段对牙齿表面的黏附和细菌共聚。然而，这种蛋白质尚未被用作抑制剂虚拟策略搜索的靶点。基于预测的结合亲和力、类药性和毒性，选择了分子并评估它们降低 黏附的能力。对 883,551 种分子进行了虚拟筛选；还对成纤维细胞进行了细胞毒性分析、 黏附研究、扫描电子显微镜分析细菌完整性以及分子动力学模拟。我们发现了三种无细胞毒性的分子 ZINC19835187（ZI-187）、ZINC19924939（ZI-939）和 ZINC19924906（ZI-906），它们能抑制约 90%的 在聚苯乙烯微孔板上的黏附。300 纳秒的分子动力学模拟显示了 ZI-187 与 Ag I/II 之间相互作用的稳定性（PDB：3IPK）。这项工作提供了新的针对 Ag I/II 的分子，具有抑制 在聚苯乙烯微孔板上黏附的能力。
