LANGEVIN DYNAMICS SIMULATION OF LIPID KINASE MUTATIONS IN CANCER

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 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. 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.