文献类型：期刊文献

中文题名：Computational Investigations about the Effects of Heteromolecular Aggregation on Bioactivities:a Case of Neonicotinoids and Water

作者：Shuang Xia[1];Jiagao Cheng[1];Yue Feng[1];Xusheng Shao[1];Haibin Luo[2];Zhiping Xu[1];Xiaoyong Xu[1];Zhong Li[1]

机构：[1]Shanghai Key Laboratory of Chemical Biology,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China;[2]School of Pharmaceutical Sciences,Sun Yat-Sen University,Guangzhou,Guangdong 510006,China

年份：2014

卷号：32

期号：4

起止页码：324

中文期刊名：Chinese Journal of Chemistry

外文期刊名：中国化学（英文版）

收录：CSTPCD;;Scopus;CSCD:【CSCD2013_2014】；PubMed;

基金：We thanks for the financial supports from the Na-tional Natural Science Foundation of China(No.21172070);the National Key Technology R&D Pro-gram of China(No.2011BAE06B05);the National High Technology Research Development Program of China(No.2011AA10A207);the National Basic Re-search Program of China(No.2010CB126100);the Fundamental Research Funds for the Central Universi-ties(No.222201314006).

语种：英文

中文关键词：hetero-aggregation;water-bridge;neonicotinoids;quantitative structure-activity relationship(QSAR);pharmacophore

摘要：Molecular aggregation state of bioactive compounds plays a key role in bio-interactive procedure.Diverse ag-gregation states of bioactive compounds contribute to different biological or chemical properties.Water-bridge,as the simple hetero-molecular aggregation,has been found bridging the binding between many bioactive compounds and their targets through hydrogen bonding network,e.g.in the recognition of neonicotinoids with insect nAChRs.To better understanding the roles of water-bridge on bioactivities of compounds,an approach of hetero-dimeric ag-gregation with water was proposed.Quantitative structure-activity relationship(QSAR)and pharmacophore mod-eling investigations were applied on 19 neonicotinoids,as well as their aggregates with water.The aggregate-based CoMSIA,PHASE and linear QSAR models presented better statistical significance and predictabilities than the monomer ones,which indicated that the bioactivities correlated with the aggregate properties and water bridged hy-drogen bond of the active site.All results revealed the essential roles of water-bridge in ligand recognition,which should be considered in future ligand design and optimization.