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: 8171866
• 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: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171866
• 关键词: Amino Acids; Automobile Driving; Computer Retrieval of Information on Scientific Projects Database; Funding; Grant; Growth; Homologous Gene; Institution; Lipids; Malignant Neoplasms; Molecular; Mutation; PIK3CA gene; PIK3CG gene; Phosphotransferases; Play; Proteins; Research; Research Personnel; Resources; Roentgen Rays; Role; Running; Source; Structure; United States National Institutes of Health; 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. 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. 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。子项目及 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。 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。