LANGEVIN DYNAMICS SIMULATION OF LIPID KINASE MUTATIONS IN CANCER

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 脂蛋白激酶突变在推动癌症生长方面发挥着重要作用。我们建议利用其同源物--I类脂蛋白激酶PIK3CG的X射线晶体结构来探索乳腺癌中I类脂蛋白激酶PIK3CA中氨基酸变化突变的潜在分子机制。我们要求资源用CHARMM对七个突变和三个野生型结构进行10 ns的朗之万动力学模拟，以阐明在癌症中产生异常、高活性蛋白质的结构变化。

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.