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OALib Journal期刊
ISSN: 2333-9721
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虚拟筛选技术辅助sert抑制剂高通量筛选模型的建立及应用
, PP. 1116-1121
Keywords: 新药发现,构效关系,5-羟色胺转运体抑制剂
Abstract:
为提高化合物筛选效率、发现更多5-羟色胺转运体(serotonintransporter,sert)抑制剂,本研究选择与中枢神经系统5-羟色胺(5-hydroxytryptamine,5-ht)能神经元具有极高相似性、能分泌5-ht、表达腺苷受体a3(a3ar)的rbl-2h3细胞,采用荧光底物asp+进行sert再摄取抑制率检测,建立生物筛选sert抑制剂的模型。在大规模的化合物库中,基于配体的虚拟筛选技术,采用贝叶斯分类方法与分子指纹相似度检索筛选出待筛化合物;进一步结合生物筛选方法进行验证,找到具有sert抑制活性的全新结构化合物。研究表明asp+检测方法有效降低环境生物危害性、检测效率高,而将生物筛选和虚拟筛选两者有机结合明显提高了筛选的效率。
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