LANGEVIN DYNAMICS SIMULATION OF LIPID KINASE MUTATIONS IN CANCER

LANGEVIN DYNAMICS 模拟癌症中的脂质激酶突变

• 批准号: 8364284
• 负责人: Rachel Karchin
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364284
• 关键词: Amino Acids; Automobile Driving; Biomedical Research; Funding; Grant; Growth; High Performance Computing; Homologous Gene; Lipids; Malignant Neoplasms; Molecular; Mutation; National Center for Research Resources; PIK3CA gene; PIK3CG gene; Phosphotransferases; Play; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Roentgen Rays; Role; Running; Source; Structure; United States National Institutes of Health; cost; lipid I; malignant breast neoplasm; mutant; simulation

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. Lipid kinase mutations play an important role in driving cancer growth. We propose to explore the underlying molecular mechanisms of amino acid changing mutations seen in breast cancers in the Class I lipid kinase PIK3CA using the X-ray crystal structure of its homolog, the Class I lipid kinase PIK3CG. We request resources to run 10ns Langevin dynamics simulations of seven mutant and three wild-type structures with CHARMM to elucidate the structural changes that produce an abnormal, hyperactive protein in cancer.

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。 脂质激酶突变在促进癌症生长中起重要作用。我们建议使用其同源物的X射线晶体结构，即I类脂质激酶PIK3CG的X射线晶体结构。我们要求资源运行七个突变体和三个具有CHARMM的野生型结构的10NS Langevin动力学模拟，以阐明在癌症中产生异常，多活跃蛋白的结构变化。