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.

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