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

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， 因此可以在其他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。 由于病毒繁殖迅速，突变率高，它们可以迅速适应新的 宿主和发展疫苗抗性，使适应性的机制的理解， 进化对人类健康至关重要。拟议的研究是一种系统的方法， 阐明噬菌体适应性蛋白质进化背后的分子机制。我们将 利用计算机模拟来定量估计单个氨基酸变化的影响 蛋白质的相互作用和稳定性，从而提供深入了解适应性的机制， 进化 我们将研究适应性和结合亲和力的变化之间可能的相关性。的 拟议的研究将提供详细的了解分子机制负责 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 是提出可能的新的适应性突变，这些突变在实验中还没有发现。 在供资期间获得的初步数据将用于生成R 01提案， 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.