ＳＵＭＯ：ＳＢＭのタンパク質　－　タンパク質相互作用阻害剤の発見

自从这个项目开始以来，我们已经开发了一种计算方法来有效地针对蛋白质-蛋白质相互作用，这是目前药物发现中的一个热门话题。相扑-SIM相互作用在相扑过程中是必不可少的，目前仍知之甚少。因此，需要一种化学探针来研究这种相互作用。我们已经证明了以SUMO-SIM与类药物化合物的相互作用为靶点抑制和刺激PPI的可行性。这些结果已经发表在两个不同的出版物上。考虑到这些有希望的结果，在这些分析方法的发展之后，建立了一个中等吞吐量的筛选实验，并确定了可能具有更有希望的临床应用前景的新型化合物。虽然该项目现已终止，但它为未来的研究工作开辟了一条道路，因为这些化合物对于优化分析SUMO-SIM相互作用和评估临床应用(癌细胞的化学和放射增敏)是有意义的。此外，与此研究平行的是，我们开发并评估了一种利用静电学进行药物发现的新方法，该方法针对蛋白质-蛋白质相互作用。这一新方法也在SAMPL4虚拟筛选挑战中使用，并帮助获得了最高排名分数。

Since the start of this project we have developed a computational approach to efficiently target protein-protein interactions, currently a hot topic in drug discovery. The sumo-sim interaction is essential in sumoylation and remains poorly understood. Therefore there is a need for a chemical probe to investigate this interaction. We have demonstrated the feasibility to target the SUMO-SIM interaction with druglike compounds for PPI inhibition as well as stimulation. These results have been published into 2 different publications. Given these promising results and after the development of the assays, a medium throughput screening experiment was set up and novel classes of compounds were identified that have possibly a more promising future for clinical usage. While this project is now terminated, it has opened a path to future research efforts as these compounds are interesting for optimization to analyse the sumo-SIM interactions and evaluate clinical usage (chemo and radio sensitization of cancer cells).Furthermore parallel with this research a novel method to utilize electrostatics for drug discovery targeting protein-protein interactions was developed and evaluated. This new method was also employed during the SAMPL4 virtual screening challenge and helped in obtained the highest ranking score.