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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 A.目标 尽管我们对烟碱的基本生物学的理解取得了巨大进步 乙酰胆碱受体，挑战仍在发展新的治疗剂。 提出的工作 在这个协作中，项目在强大的合作基础上有很大的建立（Henchman等，。 2003 a，b; Ivanov等，2007； Cheng等，2007； Wang等，2008）， 药物发现的方向用于治疗多种人类疾病。 这是 有望在开拓计算的基础上大幅提高生产率 特别是正弦组的对接工作（Gao等，2003; Wang等，2003）。 分子动力学模拟和加速分子动力学模拟将是 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。 结果将进行分析以加深我们 了解这些受体的正常和病理活性。 这个关键目标 合作的新阶段将是使用采样构象以及新兴的构象 NBCR工作流程工具作为对接小分子的目标，以暗示铅 药物发现的化合物。