MOD THE STRUCT & DYN OF NICOTINIC ACETYLCHOLINE RECEPTORS:

修改结构

• 批准号: 8362793
• 负责人: JAMES ANDREW MCCAMMON
• 金额: $ 3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362793
• 关键词: Biology; Biomedical Computing; Collaborations; Docking; Funding; Goals; Grant; Homologous Protein; Lead; Molecular Conformation; Motion; National Center for Research Resources; Nicotinic Receptors; Phase; Principal Investigator; Productivity; Research; Research Infrastructure; Resources; Sampling; Source; United States National Institutes of Health; Work; cost; drug discovery; human disease; molecular dynamics; novel therapeutics; receptor; small molecule; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A. Objectives Despite many great advances in our understanding of the fundamental biology of nicotinic acetylcholine receptors, challenges remain to develop new therapeutics. The work proposed in this collaborative project builds significantly on a strong collaboration (Henchman et al., 2003 a,b; Ivanov et al., 2007; Cheng et al., 2007; Wang et al., 2008), taking it in the direction of drug discovery for the treatment of a variety of human diseases. This is expected to enable a great increase in productivity, building on pioneering computational docking efforts of the Sine group in particular (Gao et al., 2003; Wang et al., 2003). Molecular dynamics simulations and accelerated molecular dynamics simulations will be further developed and applied to probe the internal motions of nicotinic acetylcholine receptors and homologous proteins. The results will be analyzed to deepen our understanding of the normal and pathological activity of these receptors. A key goal of this new phase of collaboration will be the use of the sampled conformations along with emerging NBCR workflow tools as targets for the docking of small molecules to suggest lead compounds for drug discovery.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 A. 目标 尽管我们对烟碱的基本生物学的理解取得了许多重大进展 乙酰胆碱受体，开发新疗法仍然面临挑战。 拟议的工作 在这个合作项目中，很大程度上建立在强有力的合作之上（Henchman 等人， 2003年a、b；伊万诺夫等人，2007；程等人，2007； Wang 等人，2008），将其纳入 治疗多种人类疾病的药物发现方向。 这是 预计将在开创性计算的基础上大幅提高生产力 特别是 Sine 小组的对接工作（Gao 等，2003；Wang 等，2003）。 分子动力学模拟和加速分子动力学模拟将 进一步开发并应用于探测烟碱乙酰胆碱的内部运动 受体和同源蛋白。 我们将对结果进行分析，以加深我们的认识 了解这些受体的正常和病理活性。 此次活动的一个关键目标 合作的新阶段将是使用采样的构象以及新兴的构象 NBCR 工作流程工具作为小分子对接的目标以建议先导 用于药物发现的化合物。