Computer-aided development of stronger channel blockers against polysaccharide transporter Wza

通过分子对接、量子力学/分子力学计算和分子动力学，结合单分子实验数据，已有的抑制剂与蛋白质WzaK30的结合部位得到了广泛的阐明。在此基础上，设计、合成和测试了新一代WzaK30缓蚀剂。其中一些化合物显示出与蛋白质结合亲和力的提高。初步计算研究揭示了这些新分子与蛋白质的一种新的结合模式。在计算、单分子生物物理学、微生物学等方面的进一步分析目前正在进行中。我预计，新的粘合剂不仅将在抗菌研究中带来新的可能性，而且将在单分子传感方面带来新的可能性。

The binding sites of existing inhibitors to protein WzaK30 have been extensively elucidated by using molecular docking, quantum mechanics/molecular mechanics calculations and molecular dynamics in combination with data obtained from single-molecule experiments. On the basis of the results, next-generation of WzaK30 inhibitors have been designed, synthesised and tested. Some of these compounds showed improved binding affinities to the protein. Preliminary computational studies revealed a new binding mode of these new molecules to the protein. Further analysis in computation, single-molecule biophysics, microbiology, etc. are currently ongoing. I expect that the new binders would bring new possibilities in not only antibacterial research but also single-molecule sensing.