Global Analysis of Small Molecule Binding to Related Protein Targets
Global Analysis of Small Molecule Binding to Related Protein Targets
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DOI：
10.1371/journal.pcbi.1002333
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发表时间：
2012-01-01
影响因子：
4.3
通讯作者：
Overington, John P.
中科院分区：
文献类型：
--
作者：
Kruger, Felix A.;Overington, John P.
我们报道了整合药理学数据和同源性信息，用于小分子结合相关靶点的大规模分析。小分子结合的差异已被评估为策展成对的人类与大鼠同源物，也为最近分化的人类相似物。我们的分析表明，在一般情况下，小分子结合是保守的对人与大鼠的同源物。通过统计检验，我们发现了少量人类和大鼠之间小分子结合不同的情况，其中一些已经在文献中报道过。物种特异性药理学知识可以有利于药物发现，其中大鼠经常被用作模型系统。对于人类的类似物，我们证明了序列同一性和具有等效亲和力的小分子结合之间的全局相关性。我们的发现提供了一个关于小分子结合和序列分化的初始通用模型，为预测和预测靶标家族内选择性的通用模型奠定了基础。
We report on the integration of pharmacological data and homology information for a large scale analysis of small molecule binding to related targets. Differences in small molecule binding have been assessed for curated pairs of human to rat orthologs and also for recently diverged human paralogs. Our analysis shows that in general, small molecule binding is conserved for pairs of human to rat orthologs. Using statistical tests, we identified a small number of cases where small molecule binding is different between human and rat, some of which had previously been reported in the literature. Knowledge of species specific pharmacology can be advantageous for drug discovery, where rats are frequently used as a model system. For human paralogs, we demonstrate a global correlation between sequence identity and the binding of small molecules with equivalent affinity. Our findings provide an initial general model relating small molecule binding and sequence divergence, containing the foundations for a general model to anticipate and predict within-target-family selectivity.