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 并且子项目的主要研究者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。 脂质激酶突变在驱动癌症生长中发挥着重要作用。我们建议使用其同源物 I 类脂质激酶 PIK3CG 的 X 射线晶体结构来探索乳腺癌中 I 类脂质激酶 PIK3CA 氨基酸改变突变的潜在分子机制。我们请求资源使用 CHARMM 对七个突变体和三个野生型结构进行 10ns Langevin 动力学模拟，以阐明在癌症中产生异常、高活性蛋白质的结构变化。