COBRE: UID: PILOT: MOLECULAR MECHANISMS FOR PROTEIN EVOLUTION IN BACTERIOPHAGE

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。 由于病毒产生速度快，变异率高，它们可以迅速适应新的 宿主和发展疫苗抗药性，了解适应的机制 进化对人类健康很重要。拟议的研究是一种系统化的方法来 阐明噬菌体适应性蛋白质进化背后的分子机制。我们会 利用计算机模拟来定量估计单一氨基酸变化的影响 关于蛋白质的相互作用和稳定性，从而提供了对适应性机制的洞察 进化论。 我们将调查适应性变化和结合亲和力之间的可能相关性。这个 拟议中的研究将提供对导致 噬菌体中的适应性蛋白质进化。这项研究有可能为 蛋白质稳定性和生物适应性之间的预测关系，这将提高我们理解和应对病毒适应的能力。拟议研究的长期目标 是为了提出可能的新的适应性突变，这些突变还没有在实验中看到。 在资助期内获得的初步数据将用于生成R01建议书，以 美国国立卫生研究院。

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. Since viruses generate rapidly and have high mutation rates, they can quickly adapt to new host and develop vaccine resistance, making an understanding of the mechanisms for adaptive evolution important for human health. The proposed research is a systematic approach to elucidate molecular mechanisms behind adaptive protein evolution in bacteriophage. We will utilize computer simulations to quantitatively estimate the effect of single amino acid changes on protein interactions and stability, and thus provide insight into the mechanisms of adaptive evolution. We will investigate the possible correlation between changes in fitness and binding affinity. The proposed research will provide detailed insight into the molecular mechanisms responsible for adaptive protein evolution in bacteriophage. This research has the potential to pave the way for predictive relationships between protein stability and biological fitness, which would improve our ability to understand and respond to viral adaptation. A long-term goal of the proposed research is to suggest possible new adaptive mutations that have not been seen experimentally. Preliminary data obtained during the funding period will be used to generate an R01 proposal to the National Institutes of Health.