CORRELATED MOTIONS AND ALLOSTERY

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。 Allostery描述了由于扰动而在一个位点改变的蛋白质功能 在另一个网站。变构的一种机制涉及相关运动，其可以 即使在没有实质性构象变化的情况下也会发生。我们提出了一种新 方法，“MutInf”，用于从平衡中识别统计上显著的相关运动 分子动力学模拟。然后我们将这种方法应用于一些蛋白质 为了提供对变构机制的深入了解并鉴定新的变构途径， 蛋白质如白细胞介素-2、泛素结合酶（E2）UBCH 5 B、Pin-1 WW结构域和半胱天冬酶-1。我们还开发了一种新的方法比较构象合奏从分子动力学模拟使用信息理论度量，并已应用此检查翻译后修饰和变构。

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. Allostery describes altered protein function at one site due to a perturbation at another site. One mechanism of allostery involves correlated motions, which can occur even in the absence of substantial conformational change. We present a novel method, "MutInf", to identify statistically significant correlated motions from equilibrium molecular dynamics simulations. We then applied this method to a number of proteins to provide insights into allosteric mechanisms and identify novel allosteric pathways, proteins such as interleukin-2, ubiquitin conjugating enzyme (E2) UBCH5B, the Pin-1 WW domain, and caspase-1. We also have developed a novel method of comparing conformational ensembles from molecular dynamics simulations using an information-theoretic metric, and have applied this to examine post-translational modifications and allostery.