Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome p450 active sites.
Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome p450 active sites.
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发表时间：
2001-07
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通讯作者：
Sean Ekins;Marcel J. de Groot;Jeffrey P. Jones
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作者：
Sean Ekins;Marcel J. de Groot;Jeffrey P. Jones
构效关系（SAR），三维构效关系（3D-QSAR），和药效团代表有用的工具，在理解细胞色素P450（CYP 450）活性位点的晶体结构的情况下，这些人类酶。这些方法在过去的30年中得到了发展，因此它们现在正被应用于许多工业和学术实验室，仅用于此目的。这种计算方法有助于理解底物和抑制剂与主要人CYP 1A 2、2B 6、2C 9、2D 6、3A 4以及其他CYP的结合，并补充了这些酶的同源性模型。类似地，这些方法可能有助于我们理解归纳法。这篇综述详细介绍了药效团和3D-QSAR技术的发展，这是现在被更广泛地用于建模CYP的审查还将描述如何这样的方法可能会进一步影响我们的活性位点的知识，这些无所不在的重要酶。
Structure activity relationships (SAR), three-dimensional structure activity relationships (3D-QSAR), and pharmacophores represent useful tools in understanding cytochrome P450 (CYP) active sites in the absence of crystal structures for these human enzymes. These approaches have developed over the last 30 years such that they are now being applied in numerous industrial and academic laboratories solely for this purpose. Such computational approaches have helped in understanding substrate and inhibitor binding to the major human CYPs 1A2, 2B6, 2C9, 2D6, 3A4 as well as other CYPs and additionally complement homology models for these enzymes. Similarly, these approaches may assist in our understanding of CYP induction. This review describes in detail the development of pharmacophores and 3D-QSAR techniques, which are now being more widely used for modeling CYPs; the review will also describe how such approaches are likely to further impact our active site knowledge of these omnipresent and important enzymes.