CSAR benchmark exercise of 2010: combined evaluation across all submitted scoring functions.
CSAR benchmark exercise of 2010: combined evaluation across all submitted scoring functions.
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DOI：
10.1021/ci200269q
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发表时间：
2011-09-26
影响因子：
5.6
通讯作者：
Carlson HA
中科院分区：
文献类型：
--
作者：
Smith RD;Dunbar JB Jr;Ung PM;Esposito EX;Yang CY;Wang S;Carlson HA
作为社区结构-活性资源（CSAR）中心的一部分，利用文献中实验确定的Kd或Ki信息组装了一组343个高质量的蛋白质-配体晶体结构。我们鼓励社区通过他们选择的任何方法对复合物的晶体结构进行评分。该练习的目的是（1）评估该领域目前从结构预测活动的能力，以及（2）调查似乎阻碍评分的复合物和方法的性质。总共提交了19种不同的方法，其中包括来自16个参与组的64组评分的许多参数变化。使用线性回归和非参数检验将分数与实验值相关联。各种方法与实验的相关性范围为R2 = 0.58-0.12，斯皮尔曼ρ = 0.74-0.37，Kendall τ = 0.55-0.25，中位无符号误差= 1.00-1.68 pKd单位。所有类型的评分函数-基于力场的，基于知识的，和神经网络-都有高相关性和低相关性的例子，没有显示任何特定方法的偏见/优势。所有参与者的数据被合并，以确定63个在大多数评分方法中得分较低的复合物和123个在大多数评分方法中得分较高的复合物。使用Wilcoxon秩和检验比较两组，以评估配体和蛋白质的>400种物理化学性质的分布中的任何显著差异。得分不佳的复合物被发现有配体的大小相同的那些在得分良好的复合物，但氢键和扭转应变显着不同。这些比较点需要CSAR开发数据集的同源系列的一系列氢键和疏水特性和一系列的旋转键。
As part of the Community Structure-Activity Resource (CSAR) center, a set of 343 high-quality, protein–ligand crystal structures were assembled with experimentally determined Kd or Ki information from the literature. We encouraged the community to score the crystallographic poses of the complexes by any method of their choice. The goal of the exercise was to (1) evaluate the current ability of the field to predict activity from structure and (2) investigate the properties of the complexes and methods that appear to hinder scoring. A total of 19 different methods were submitted with numerous parameter variations for a total of 64 sets of scores from 16 participating groups. Linear regression and nonparametric tests were used to correlate scores to the experimental values. Correlation to experiment for the various methods ranged R2 = 0.58–0.12, Spearman ρ = 0.74–0.37, Kendall τ = 0.55–0.25, and median unsigned error = 1.00–1.68 pKd units. All types of scoring functions—force field based, knowledge based, and empirical—had examples with high and low correlation, showing no bias/advantage for any particular approach. The data across all the participants were combined to identify 63 complexes that were poorly scored across the majority of the scoring methods and 123 complexes that were scored well across the majority. The two sets were compared using a Wilcoxon rank-sum test to assess any significant difference in the distributions of >400 physicochemical properties of the ligands and the proteins. Poorly scored complexes were found to have ligands that were the same size as those in well-scored complexes, but hydrogen bonding and torsional strain were significantly different. These comparisons point to a need for CSAR to develop data sets of congeneric series with a range of hydrogen-bonding and hydrophobic characteristics and a range of rotatable bonds.
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影响因子：
5.6
作者：
Dunbar JB Jr;Smith RD;Yang CY;Ung PM;Lexa KW;Khazanov NA;Stuckey JA;Wang S;Carlson HA
通讯作者：
Carlson HA
影响因子：
14.9
作者：
Davis IW;Leaver-Fay A;Chen VB;Block JN;Kapral GJ;Wang X;Murray LW;Arendall WB 3rd;Snoeyink J;Richardson JS;Richardson DC
通讯作者：
Richardson DC
影响因子：
7.3
作者：
Charifson, PS;Corkery, JJ;Walters, WP
通讯作者：
Walters, WP
影响因子：
7.3
作者：
Bissantz, C;Folkers, G;Rognan, D
通讯作者：
Rognan, D
影响因子：
7.3
作者：
Carlson HA;Smith RD;Khazanov NA;Kirchhoff PD;Dunbar JB Jr;Benson ML
通讯作者：
Benson ML