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

计算机辅助开发针对多糖转运蛋白 Wza 的更强通道阻断剂

• 批准号: 17H06912
• 负责人: Kong Lingbing
• 金额: $ 1.75万
• 依托单位: Kagawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2017
• 资助国家: 日本
• 起止时间: 2017-08-25 至 2019-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17H06912/
• 关键词: computation; Wza; transporter; polysaccharide; channel blocker; computer-aided

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.

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获得的数据，现有抑制剂与蛋白质WzaK30的结合位点已被广泛阐明。根据这些结果，下一代 WzaK30 抑制剂已被设计、合成和测试。其中一些化合物表现出改善的与蛋白质的结合亲和力。初步计算研究揭示了这些新分子与蛋白质的新结合模式。目前正在进行计算、单分子生物物理学、微生物学等方面的进一步分析。我预计新的粘合剂不仅会为抗菌研究带来新的可能性，还会为单分子传感带来新的可能性。

项目成果

Sugars and Sugar Transporters

糖和糖转运蛋白

• 发表时间: 2017
• 作者: Kozhinjampara R. Mahendran;Ai Niitsu;Lingbing Kong;Andrew R. Thomson;Richard B. Sessions;Derek N. Woolfson & Hagan Bayley;Lingbing Kong
• 通讯作者: Lingbing Kong