LANGEVIN DYNAMICS SIMULATION OF LIPID KINASE MUTATIONS IN CANCER

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 脂质激酶突变在驱动癌症生长中起重要作用。我们建议探索潜在的分子机制的氨基酸改变突变的乳腺癌中看到的I类脂质激酶PIK 3CA使用其同系物，I类脂质激酶PIK 3CG的X-射线晶体结构。我们请求资源运行10 ns朗之万动力学模拟7个突变体和3个野生型结构与CHARMM阐明的结构变化，产生异常，在癌症中的过度活跃的蛋白质。

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.