MOD THE STRUCT & DYN OF NICOTINIC ACETYLCHOLINE RECEPTORS:

修改结构

• 批准号: 7955280
• 负责人: Steven M Sine
• 金额: $ 0.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955280
• 关键词: Biology; Biomedical Computing; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Docking; Funding; Goals; Grant; Homologous Protein; Institution; Lead; Molecular Conformation; Motion; Nicotinic Receptors; Phase; Productivity; Research; Research Personnel; Resources; Sampling; Source; United States National Institutes of Health; Work; 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. 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. 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 A. 目标 尽管我们对烟碱乙酰胆碱受体的基础生物学的理解取得了许多巨大进展，但开发新疗法仍然面临挑战。 该合作项目中提出的工作在很大程度上建立在强有力的合作基础上（Henchman 等人，2003 a,b；Ivanov 等人，2007；Cheng 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。 尤其是在 Sine 小组开创性的计算对接工作的基础上，这预计将大大提高生产率（Gao 等人，2003 年；Wang 等人，2003 年）。 分子动力学模拟和加速分子动力学模拟将进一步发展并应用于探测烟碱乙酰胆碱受体和同源蛋白的内部运动。 将对结果进行分析，以加深我们对这些受体的正常和病理活性的理解。 这一新阶段合作的一个关键目标是使用采样的构象以及新兴的 NBCR 工作流程工具作为小分子对接的目标，以建议用于药物发现的先导化合物。