Use of artificial intelligence in structure-affinity correlations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) receptor ligands.
Use of artificial intelligence in structure-affinity correlations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) receptor ligands.
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使用人工智能研究 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 受体配体的结构亲和力相关性。
DOI：
10.1093/carcin/12.11.2007
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发表时间：
1991
期刊：
影响因子：
4.7
通讯作者：
Klopman,G
中科院分区：
文献类型：
--
作者：
Rannug,U;Sjögren,M;Rannug,A;Gillner,M;Toftgård,R;Gustafsson,JA;Rosenkranz,H;Klopman,G
计算机自动结构评价（CASE）程序是一个自动选择构效关系相关描述符的专家系统，已被用于分析各种配体与四氯二苯并二恶英（TCDD）受体或AhR的结合。分析了两个数据库。一个数据库包含136多环芳烃（PAH），取代二苯并二恶英，二苯并呋喃和联苯的结合亲和力测定的蔗糖密度梯度技术。其余87个化合物数据库包括PAH、硝基PAH、卤代PAH和N-杂环化合物。它们的结合亲和力通过电聚焦测定来测量。在每个训练集内，观察到TCDD受体的亲和力与CASE程序鉴定的相关分子片段之间的显著相关性。在卤代芳烃中，含有横向卤素和纵向氢的片段对TCDD受体结合很重要。多环芳烃和杂环化合物的片段，最活化的TCDD受体结合被发现含有经典的“海湾”区域，实际上是相同的片段，以前被发现与致癌性。结果发现，从PAH和杂环化合物的激活片段中发现的卤代化合物，如二苯并二恶英，二苯并呋喃和联苯中的那些不同。对这些数据的一种解释是，两个不同的识别位点可能参与AhR结合。
The Computer-Automated Structure Evaluation (CASE) Program, an expert system that automatically selects relevant descriptors for structure-activity relationships, has been used to analyze the binding of various ligands to the tetrachloro-dibenzo-p-dioxin (TCDD) receptor orAhreceptor. Two databases were analyzed. One database contained 136 polycyclic aromatic hydrocarbons (PAH), substituted dibenzo-p-dioxins, dibenzofurans and biphenyls whose binding affinities were measured by a sucrose density gradient technique. The other 87 compound database contained PAH, nitro-PAH, halo-PAH andN-heterocycles. Their binding affinities were measured by the electrofocusing assay. Within each training set significant correlations between the affinity for the TCDD receptor and relevant molecular fragments identified by the CASE program were observed. Among the halogenated aromatic hydrocarbons, fragments containing lateral halogens and a longitudinal hydrogen appeared important for TCDD receptor binding. The fragments of PAH and heterocyclic compounds that were most activating with respect to TCDD receptor binding were found to contain the classical ‘bay’ region and were in fact identical to the fragments found previously to be related to carcinogenkity. It was found that the activating fragments from PAH and heterocyclic compounds were different from those found within the halogenated compounds such as dibenzo-p-dioxins, dibenzofurans and biphenyls. One interpretation of the data is that two different recognition sites may be involved inAhreceptor binding.