MOLECULAR DYNAMICS STUDIES OF ALPHA CRYSTALLIN

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。子项目及 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。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 ?-晶状体蛋白是哺乳动物透镜的主要结构蛋白，由两个亚基组成，A和？B。除了其作为结构蛋白的作用之外，α-晶状体蛋白有助于透镜的折射性质，并且已经显示出表现出分子伴侣活性。在溶液中，它以具有分子量分布的聚集体形式存在。聚集体大小的这种广泛分布被认为是导致蛋白质结晶尝试失败的原因。计算建模？-晶体蛋白聚集体和亚基之间相互作用的研究对于确定晶体蛋白的三级和四级结构是必不可少的。而这一点，也可以说是一种引导，一种引导。我们目前的亚基模型是通过折叠识别方法建立的，然后通过分子力学程序进行改进。什么模特？-根据表面互补原理，采用对接方法构建了晶体蛋白二聚体，并利用分子动力学程序NAMD和VMD模拟了晶体蛋白二聚体的平衡态。此外，Ligplot程序用于研究亚基之间的相互作用。初步的分子动力学研究和操纵动力学模拟计算已经进行了一纳秒的调光器。这些计算表明氢键和疏水相互作用在亚基结合中起着非常重要的作用;初步模型表明Trp 60在？B包含在亚基之间的相互作用中，这与以前的实验结果一致[1]。为了扩展这项工作，并获得进一步的细节亚基相互作用，分子动力学研究两个较大的？需要晶体蛋白聚集体和更长的模拟时间，例如1微秒。我们认为，NCSA Teragrid集群是这些研究的宝贵资源。参考：1. McDermott，M.，基耶萨河罗伯茨，J.E.，Dillon，J.（1991）Biochemistry 30，8653-8660

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. ?-crystallin is the major structural protein of the mammalian lens and consists of two subunits, ?-A and ?-B. In addition to its role as a structural protein, a-crystallin contributes to the refractive properties of the lens and has been shown to exhibit chaperone activity. In solution, it exists in aggregate form with a distribution of molecular weights. This broad distribution of aggregate size is thought to be responsible for the unsuccessful attempts at crystallizing the protein. Computational modeling of ?-crystallin aggregates and studies on the interactions between subunits are essential for determining the tertiary and quaternary structures of ?-crystallin and may give guidance toward successful crystallization. Our current models for the subunits are built up by the fold recognition method and then refined by molecular mechanics programs. Models for ?-crystallin dimers are built up by the docking method according to the surface complementary principle and molecular dynamic programs NAMD and VMD are used to simulate the dimers at equilibrium. In addition, the Ligplot program is used to study the interactions between the subunits. Preliminary molecular dynamic studies and steered dynamic simulations calculations have been carried out for one nanosecond on the dimmer. These calculations indicate that hydrogen bonds and hydrophobic interactions play very important roles in subunit binding; the preliminary model indicates Trp60 in ?-B is included in the interactions between the subunits and this is in agreement with previous experimental results[1]. In order to extend this work and obtain further details on subunit interactions, molecular dynamic studies on both larger ?-crystallin aggregates and with longer simulation time, e.g. one microsecond, are needed. We believe that the NCSA Teragrid cluster is an invaluable resource for these studies. Reference: 1. McDermott, M., Chiesa, R., Roberts, J.E., Dillon, J. (1991) Biochemistry 30, 8653-8660