化学
化学空间
虚拟筛选
药物发现
药效团
计算生物学
化学信息学
相似性(几何)
分子动力学
化学
化学数据库
计算机科学
生物信息学
生物
生物化学
计算化学
人工智能
图像(数学)
出处
期刊:Chimia
日期:2022-12-21
卷期号:76 (12): 1045-1045
被引量:1
标识
DOI:10.2533/chimia.2022.1045
摘要
Similar drug molecules often have similar properties and activities. Therefore, quantifying molecular similarity is central to drug discovery and optimization. Here I review computational methods using molecular similarity measures developed in my group within the interdisciplinary network NCCR TransCure investigating the physiology, structural biology and pharmacology of ion channels and membrane transporters. We designed a 3D molecular shape and pharmacophore comparison algorithm to optimize weak and unselective inhibitors by scaffold hopping and discovered potent and selective inhibitors of the ion channels TRPV6 and TRPM4, of endocannabinoid membrane transport, and of the divalent metal transporters DMT1 and ZIP8. We predicted off-target effects by combining molecular similarity searches from different molecular fingerprints against target annotated compounds from the ChEMBL database. Finally, we created interactive chemical space maps reflecting molecular similarities to facilitate the selection of screening compounds and the analysis of screening results. These different tools are available online at https://gdb.unibe.ch/tools/.
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