A pharmacophore hypothesis and computationally optimized lead compounds for VKORC1

机译：VKORC1的药效基团假设和计算优化的先导化合物

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Warfarin is a popular pharmaceutical anticoagulant that targets the vitamin K epoxide reductase complex sub-unit 1, encoded by the gene VKORC1, but warfarin can be dangerous since it can cause bleeding. A first step in finding better anticoagulants that target the same enzyme is structure based lead molecule optimization using computational tools. This is possible because the tertiary structure of a bacterial homologue of VKORC1 is known. Lead molecules derived from this process can be selected for superior ADMET properties and high binding affinity. This work documents two such molecules, informally named pyracoumarols, that could be useful lead molecules for real world testing and synthesis. These molecules have pretty good predicted ADMET qualities and better predicted binding affinity than warfarin. A pharmacophore hypothesis is proposed that describes the ligands that will effectively dock with VKORC1.

机译：华法林是一种流行的药物抗凝剂，其靶向由VKORC1基因编码的维生素K环氧还原酶复合物亚基1，但华法林可能会引起出血，因此很危险。寻找针对相同酶的更好抗凝剂的第一步是使用计算工具进行基于结构的先导分子优化。这是可能的，因为已知VKORC1的细菌同源物的三级结构。可以选择源自此过程的先导分子，以获得卓越的ADMET性能和高结合亲和力。这项工作记录了两个这样的分子，非正式地命名为吡喃香酚，它们可能对现实世界的测试和合成有用。与华法林相比，这些分子具有相当好的ADMET质量预测值和更好的预测结合亲和力。提出了一种药效团假说，该假说描述了将与VKORC1有效对接的配体。

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《IEEE International Conference on Computational Advances in Bio and Medical Sciences》|2017年|1-6|共6页
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Jacob Porter;
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Lead; Proteins; Drugs; Lead compounds; Optimization; Hydrogen; Tools;

机译：铅;蛋白质;药物;铅化合物;优化;氢;工具;

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A pharmacophore hypothesis and computationally optimized lead compounds for VKORC1

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