RT Journal Article
SR Electronic
T1 Big data and artificial intelligence discover novel drugs targeting proteins without 3D structure and overcome the undruggable targets
JF Stroke and Vascular Neurology
JO Stroke Vasc Neurol
FD BMJ Publishing Group Ltd
SP 381
OP 387
DO 10.1136/svn-2019-000323
VO 5
IS 4
A1 Huiqin He
A1 Benquan Liu
A1 Hongyi Luo
A1 Tingting Zhang
A1 Jingwei Jiang
YR 2020
UL http://svn.bmj.com/content/5/4/381.abstract
AB The discovery of targeted drugs heavily relies on three-dimensional (3D) structures of target proteins. When the 3D structure of a protein target is unknown, it is very difficult to design its corresponding targeted drugs. Although the 3D structures of some proteins (the so-called undruggable targets) are known, their targeted drugs are still absent. As increasing crystal/cryogenic electron microscopy structures are deposited in Protein Data Bank, it is much more possible to discover the targeted drugs. Moreover, it is also highly probable to turn previous undruggable targets into druggable ones when we identify their hidden allosteric sites. In this review, we focus on the currently available advanced methods for the discovery of novel compounds targeting proteins without 3D structure and how to turn undruggable targets into druggable ones.