LARGE SCALE MEASUREMENT OF EPISTASIS TO IDENTIFY MUTATIONS THAT STABILIZE PROTEI

大规模测量上位性以鉴定稳定蛋白质的突变

• 批准号: 8365793
• 负责人: STANLEY FIELDS
• 金额: $ 2.18万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365793
• 关键词: Biology; Chemosensitization; Funding; Fungal Genome; Genetic Epistasis; Goals; Grant; Measurement; Measures; Metric; Mutation; National Center for Research Resources; Pharmacologic Substance; Principal Investigator; Protein Engineering; Proteins; Proteus; Research; Research Infrastructure; Resources; Source; United States National Institutes of Health; Variant; base; cost; fitness; meetings; mutant; success

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Engineering proteins for enhanced stability is often critical for their industrial or pharmaceutical use, but experimental and computational efforts to accomplish this goal have met with limited success. We identified stabilizing mutations in a WW domain based solely on a measurement of protein fitness for more than 47,000 variants, and the use of these fitness measurements to calculate more than 5,000 epistastic relationships. We introduce a new metric, termed ?partner potentiation,? which is a measure of the mean epistasis effect that a mutation imparts to other mutations when combined in a double mutant. This metric allowed us to infer the identity of 15 stabilizing mutations within the WW domain.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 提高稳定性的工程蛋白对于其工业或药物使用通常至关重要，但是实现这一目标的实验和计算工作取得了有限的成功。 我们仅基于蛋白质适应性的测量值确定了WW域中的稳定突变，超过47,000种变体，并使用这些适应性测量值来计算超过5,000个认识关系。 我们介绍了一个新的指标，称为合作伙伴的增强，？这是对平均上毒作用的量度，即在双突变体中合并时，突变会赋予其他突变。 该指标使我们能够推断出WW域内15个稳定突变的身份。