MODELING THE STRUCTURES OF PROTEINS AND PROTEIN COMPLEXES

蛋白质和蛋白质复合物结构建模

• 批准号: 6103842
• 负责人: ALASDAIR C. STEVEN
• 金额: --
• 依托单位: CENTER FOR INFORMATION TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6103842
• 关键词: chemical models; conformation; electron density; enzyme inhibitors; hydrogen bond; luteinizing hormone; membrane proteins; protein structure; rhodopsin

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.

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。的结合 类黄酮抑制剂细胞周期蛋白依赖性激酶2作为模型 系统调查的计算机模拟， 允许蛋白质和配体都是柔性的。在没有 晶体结构的复杂性，这种灵活性必须是可靠的 来优化蛋白质药物。此外，各种 程序应用于对接问题，以确定优势 和不同软件包的弱点。分子建模 用于评估催化的结构要求， 人甲硫氨酸腺苷转移酶I/III的二聚化。一 手稿提交出版。分子建模是 也用于比较组合中的氨基酸呈现 两个抗酵母iso-1细胞色素c单克隆抗体之间位点 表位密切相关的抗体。一份手稿 提交出版。短螺旋的四聚体状态 花椰菜花叶病毒ORFIII产物的螺旋结构域具有 通过几种实验方法确定。的3D 对卷曲螺旋四聚体的结构进行建模， 了解α螺旋卷曲螺旋的结构原理 低聚反应几个氨基酸突变被引入到 卷曲螺旋片段基于对模型的分析， 结构对突变体结构进行了实验分析。一 手稿已提交出版。