【What The Drug: Drug Discovery Live Stream】讲座来自BioSolvel
视频知识点总结:
“……the experiment is only an experiment so that means that what we see is an interpretation of electron density……”
1. 晶体结构是否有多个Biological Assembly? 配体在不同Biological Assembly中是否有差异(PLX4720/PDB: 3C4C; ARM1/PDB: 4L2L);
2. 借助[Proteins.Plus/https://proteins.plus]检查晶体结构中配体是否被精确解析(感觉有点像B-factor)(Astex Pharmaceuticals IAP JMC文章/DOI:10.1021/acs.jmedchem.6b01877 基于这个“……the electron density of the ether side chain is not well resolved in the crystal structure which suggests it can assume a number of energetically similar conformations in the crystal structure of 7 and may not be optimal.””从而确定继续优化的方向);
3. 视频中好像还通过Proteins.Plus中的SIENA寻找其他B-raf晶体结构(通过PDB号 -> UniProt -> Structure也是可以查询到特定蛋白的所有晶体结构)并叠合,以便查看是否有差异(难道是为了寻找新的口袋并利用?)(印象中有看到过比较有配体结合的蛋白和apo 蛋白晶体结构)(欢迎知道的朋友留言)。
在之前的推文【芳香胺潜在基因毒性解决策略】也提到视频分子KIN-2787借助脲稳定高于酰胺的特点来规避芳香胺潜在基因毒性。
"The crystal structure for biological system is more like a model due to limited resolution and the fitting process"
*一起探讨,共同进步!*
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