DEVELOPMENT OF A BASIC WORK FLOW FOR PHYLOGENTIC INFERENCE OF ANCESTRAL PROTEIN

祖先蛋白质系统发育推断基本工作流程的开发

• 批准号: 8171884
• 负责人: Mari A. Watanabe
• 金额: $ 0.14万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171884
• 关键词: Address; Affect; Amino Acid Sequence; Carbohydrates; Complex; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Development; Enzymes; Funding; Goals; Grant; Institution; Light; Mechanics; Methods; Molecular Evolution; Molecular Models; Peptide Sequence Determination; Phylogenetic Analysis; Process; Protein Family; Proteins; Research; Research Personnel; Resources; Source; Structure; Techniques; To specify; United States National Institutes of Health; Work; molecular dynamics; molecular modeling; quantum; reconstruction

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. The goal of this proposal is to further develop a basic work flow to refine a phylogenetic inference of ancestral protein sequences. In general, the phylogenetic inference is a powerful technique for the study of molecular evolution, but any conclusions drawn from such studies are only as good as the accuracy of the reconstruction method. Moreover, these studies are not capable to specify structural and functional changes along molecular evolution processes. In this project, molecular modeling and computational simulation will be employed to further refine predicted ancestral protein sequences and their possible structures. The approach combines quantum mechanical and molecular dynamics studies to address the challenge. In this project, we are focusing on structures and functions of glucosidsases which are enzymes involved in breaking down complex carbohydrates. Computational refinement of predicted ancestral protein sequences and structures of glucosidsase family proteins requires an intense computation. This study possibly will shed some light on how evolutionary changes affect on structure and functions of enzymes.

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。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他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。 本提案的目标是进一步开发一个基本的工作流程，以完善祖先蛋白质序列的系统发育推断。一般来说，系统发育推断是研究分子进化的一种强有力的技术，但从这样的研究中得出的任何结论都只有重建方法的准确性。此外，这些研究不能说明结构和功能的变化，沿着分子进化过程。在这个项目中，分子建模和计算机模拟将被用来进一步完善预测的祖先蛋白质序列和它们可能的结构。该方法结合了量子力学和分子动力学研究来应对挑战。在这个项目中，我们专注于葡萄糖苷酶的结构和功能，葡萄糖苷酶是参与分解复杂碳水化合物的酶。预测的祖先蛋白质序列和葡萄糖苷酶家族蛋白质结构的计算精化需要密集的计算。这项研究可能会揭示进化变化如何影响酶的结构和功能。