Consensus scoring: A method for obtaining improved hit rates from docking databases of three-dimensional structures into proteins
Consensus scoring: A method for obtaining improved hit rates from docking databases of three-dimensional structures into proteins
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DOI：
10.1021/jm990352k
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发表时间：
1999-12-16
影响因子：
7.3
通讯作者：
Walters, WP
中科院分区：
文献类型：
--
作者：
Charifson, PS;Corkery, JJ;Walters, WP
我们提出了一项广泛的计算研究的结果，其中我们表明，在基于交叉点的共识方法中结合评分函数可以增强区分活性和非活性酶抑制剂的能力。这是在将三维结构集合对接到三种不同的药物酶的背景下说明的：p38 MAP激酶，肌苷单磷酸脱氢酶和HIV蛋白酶。通过对两种不同的对接方法和13个评分函数的分析，可以了解哪些函数单独使用和组合使用时表现良好。我们的数据表明，共识评分进一步显著减少了由单个评分函数识别的误报数量，从而显著提高了命中率。
We present the results of an extensive computational study in which we show that combining scoring functions in an intersection-based consensus approach results in an enhancement in the ability to discriminate between active and inactive enzyme inhibitors. This is illustrated in the context of docking collections of three-dimensional structures into three different enzymes of pharmaceutical interest: p38 MAP kinase, inosine monophosphate dehydrogenase, and HIV protease. An analysis of two different docking methods and thirteen scoring functions provides insights into which functions perform well, both singly and in combination. Our data shows that consensus scoring further provides a dramatic reduction in the number of false positives identified by individual scoring functions, thus leading to a significant enhancement in hit-rates.