PbsNRs:预测核受体的潜在结合剂和支架
Genhui Zheng1,2, Dingfeng Wu3, Xiuxia Wei4
1Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical College, Shanghai Institute of Infectious Disease and Biosecurity, Intelligent Medicine Institute, School of Life Sciences, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China.
一个新的网络服务器,PbsNRs,预测核受体 (NR) 结合剂和药物开发的支架. 它准确地识别了来自化学化合物和自然产品的潜在NR药物候选物和生物活性支架.
科学领域:
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
- 计算生物学 计算生物学
背景情况:
- 核受体 (NRs) 是调节基因表达的关键蛋白质,并与各种疾病有关.
- 开发有效的in silico方法来预选NR结合剂对于NR相关药物发现至关重要.
- 目前用于预测NR结合物的方法有限,这凸显了对先进计算工具的需求.
研究的目的:
- 引入PbsNRs,一个用户友好的网络服务器,用于预测核受体结合剂和支架.
- 评估PbsNRs对化学化合物和自然产品的预测性能.
- 证明PbsNRs在识别生物活性支架和指导NR相关疾病的药物发现方面的实用性.
主要方法:
- 开发PbsNRs网络服务器,使用蛋白化学建模.
- 使用化学化合物的内部和外部数据集对PbsNR性能进行系统评估.
- 对自然产品进行选,以确定NRs的生物活性化学支架.
- 使用生物传感器对NR2B1预测的生物活性和非活性天然产品进行实验验证.
主要成果:
- 对于化学化合物,PbsNR显示出强大的预测性能,ROC-AUC值为0.906 (内部) 和0.783 (外部).
- 服务器的性能优于现有的化合物-连接体相互作用工具和NR特定预测器.
- PbsNRs成功地从自然产品中确定了生物活性化学支架,并对NR2B1.1.的预测进行了验证.
结论:
- PbsNR是选潜在的治疗性NR结合物的有效工具,并发现必要的分子支架.
- 网络服务器有助于指导针对多种NR相关疾病的药物发现工作.
- PbsNR为研究人员在核受体药物开发领域提供了宝贵的资源.
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