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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项提议的目标是进一步发展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。总体而言，系统发育推断是研究分子进化的一项强有力的技术，但从这类研究中得出的任何结论都与重建方法的准确性一样好。此外，这些研究不能具体说明分子进化过程中结构和功能的变化。在这个项目中，将使用分子建模和计算模拟来进一步精炼预测的祖先蛋白质序列及其可能的结构。这种方法结合了量子力学和分子动力学的研究来应对这一挑战。在这个项目中，我们重点研究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。对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。这项研究可能会为进化变化如何影响酶的结构和功能提供一些线索。

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.