MODELING THE STRUCTURES OF PROTEINS AND PROTEIN COMPLEXES

我们一直在对接小分子(例如药物) 利用蒙特卡罗(MC)模拟将其转化为蛋白质。对象的绑定 细胞周期蛋白依赖性激酶2的类黄酮类抑制剂作为模型 用于调查计算机模拟的可靠性的系统 允许蛋白质和配体都是灵活的。在缺少 晶体结构的络合物，这样的灵活性必须可靠 处理以优化蛋白质的药物。此外，各种不同的 程序被应用于对接问题，以确定优势 以及不同软件包的缺点。分子建模 用于评估催化的结构要求和 人蛋氨酸腺苷转移酶I/III.A的二聚化 手稿被提交发表。分子建模是 也用来比较组合中的氨基酸表现形式 两株抗酵母iso-1细胞色素c单抗之间的结合 表位密切相关的抗体。一份手稿是 已提交出版。短螺旋的四聚体状态 花椰菜花叶病毒ORFIII产物的COIL结构域 由几种实验方法测定。3D 对盘绕线圈四聚体的结构进行了模拟，以便 了解阿尔法螺旋线圈的结构原理 齐聚作用。几种氨基酸突变被引入到 基于模型分析的线圈断片 结构。对突变结构进行了实验分析。一个 已提交手稿以供出版。

We have been docking small molecules (e.g., drugs) into proteins using Monte Carlo (MC) simulation. The binding of a flavonoid inhibitor to cyclin dependent kinase 2 serves as a model system to investigate the reliability of computer simulations that allow both the protein and ligand to be flexible. In the absence of a crystal structure of the complex, such flexibility must be reliably handled to optimize drugs for proteins. In addition, a variety of programs were applied to docking problems to identify strengths and weaknesses of different software packages.Molecular modeling was used to assess the structural requirements for catalysis and dimerization of human methionine adenosyltransferase I/III. A manuscript was submitted for publication.Molecular modeling was also used to compare the amino acid presentation in the combining site between two anti-yeast iso-1 cytochrome c monoclonal antibodies whose epitopes are closely related. A manuscript was submitted for publication.The tetrameric state of the short coiled coil domain of the ORFIII product of cauliflower mosaic virus has been determined by several experimental methods. The 3D structure of the coiled coil tetramer was modeled in order to understand the structural principles of the alpha-helical coiled coil oligomerization. Several amino acid mutations were introduced into the coiled coil fragment based on the analysis of the modeled structure. The mutant structures were experimentally analyzed. A manuscript was submitted for publication.