COMPUTATIONAL APPROACHES TO UNDERSTAND THE INTERACTION OF HIV-1 INTEGRASE AND I

理解 HIV-1 整合酶和 I 相互作用的计算方法

基本信息

批准号：
8171776
负责人：
Zengjian Hu
金额：
$ 0.11万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8171776
关键词：
AIDS therapy Anti-HIV Agents Binding Biological Factors Catalytic Domain Cells Chinese Herbs Chromosomes Complement Complex Computer Retrieval of Information on Scientific Projects Database DNA Drug Design Enzyme Inhibitor Drugs Enzyme Inhibitors Enzymes Exhibits Funding Genome Grant HIV HIV Protease HIV-1 HIV-1 integrase Herbal Medicine Institution Integrase Lead Life Cycle Stages Methodology Molecular Models Research Research Personnel Resources Reverse Transcriptase Inhibitors Scutellaria baicalensis Source Structure Techniques Therapeutic Uses United States National Institutes of Health Work baicalein baicalin base design drug candidate inhibitor/antagonist molecular modeling

AIDS therapy Anti-HIV Agents Binding Biological Factors Catalytic Domain Cells Chinese Herbs Chromosomes Complement Complex Computer Retrieval of Information on Scientific Projects Database DNA Drug Design Enzyme Inhibitor Drugs Enzyme Inhibitors Enzymes Exhibits Funding Genome Grant HIV HIV Protease HIV-1 HIV-1 integrase Herbal Medicine Institution Integrase Lead Life Cycle Stages Methodology Molecular Models Research Research Personnel Resources Reverse Transcriptase Inhibitors Scutellaria baicalensis Source Structure Techniques Therapeutic Uses United States National Institutes of Health Work baicalein baicalin base design drug candidate inhibitor/antagonist molecular modeling

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项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. An essential step in the life cycle of human immunodeficiency virus type 1 (HIV-1) is integration of the double-stranded retroviral DNA into the genome of the host cell. HIV- 1 integrase, the enzyme that insertors, ts the vital DNA into the host chromosome, is an attractive and rational target for anti-AIDS drug design because it is essential for HIV replication and there are no known counterparts in the host cell. Inhibitors of this enzyme have the great potential to complement the therapeutic use of HIV protease and reverse transcriptase inhibitors. Natural products have provided a source of new drug candidates for anti-AIDS therapy. The number of compounds exhibiting anti-HIV activity and isolated from natural sources has increase steadily. Baicalein and baicalin, identified components of a Chinese herbal medicine Scutellaria baicalensis Georgi, have been shown to inhibit infectivity and replication of HIV. They are therefore promising lead compounds for developing new anti-AIDS drugs. To understand how the inhibitors work and therefore design more potent and specific inhibitors, we have used molecular modeling techniques to investigate the binding modes of these inhibitors. Computational binding studies of these inhibitors, based on the crystal structure of the HIV-1 integrase catalytic domain, will be performed to study the complex structure using QM/MM methodology.

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。人类免疫缺陷病毒1型（HIV-1）生命周期的重要步骤是将双链逆转录病毒DNA整合到宿主细胞的基因组中。艾滋病病毒- 1积分酶，插入，将重要DNA插入宿主染色体的酶是一种抗AIDS药物设计的有吸引力且合理的目标，因为它对于艾滋病毒至关重要复制，宿主单元中没有已知的对应物。抑制剂酶具有补充HIV蛋白酶治疗用途的巨大潜力和逆转录酶抑制剂。天然产品提供了新的来源抗AID疗法的毒品候选人。表现出抗HIV的化合物数量从自然来源隔离的活动和隔离的稳定增长。黄氨基林和黄氨酸，鉴定出中草药的成分已显示可抑制HIV的感染性和复制。因此，他们很有希望铅化合物用于开发新的抗艾滋病药物。了解抑制剂如何工作，因此设计了更有效和特异性抑制剂，我们使用了分子建模技术以研究这些抑制剂的结合模式。这些抑制剂的计算结合研究，基于 HIV-1整合酶催化域将进行使用，以研究使用 QM/mm方法。