PROTEIN CONFORMATION SAMPLING USING ENERGY LANDSCAPE APPROACH

使用能量景观方法进行蛋白质构象采样

• 批准号: 7955248
• 负责人: Peter Guy Wolynes
• 金额: $ 0.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955248
• 关键词: Address; Affect; Amino Acids; Biomedical Computing; Computer Retrieval of Information on Scientific Projects Database; Funding; Genome; Grant; Histidine; Hydrogen; Institution; Lead; Mammalian Cell; Mass Spectrum Analysis; Methylation; Modification; Paper; Phosphopeptides; Phosphorylation; Polymers; Post-Translational Protein Processing; Protein Conformation; Proteins; Regulation; Research; Research Personnel; Resources; Sampling; Secondary Protein Structure; Serine; Side; Signal Transduction; Source; Tertiary Protein Structure; Threonine; Tyrosine; United States National Institutes of Health; glycosylation; protein protein interaction

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. In mammalian cells, proteins are initially expressed as hetero-polymers with 20 types of different amino acids. Proteins, however, often need more varieties of subunits. This greater diversity is achieved by covalent post-translational modifications such as glycosylation, methylation, or nucleotidylation. These modifications can lead to conformational changes of the proteins by perturbing their energy landscape and thereby altering their functions. In this paper, we address the energetic and structural consequence of one of the most important forms of reversible modification: phosphorylation. In phosphopeptides, the side chain polar hydrogens of serine, threonine, tyrosine, and histidine can be replaced by phosphoryl groups. Phosphorylation occurs quite frequently in signal transduction regulation and is increasingly being noticed throughout the genome due to the advancements of mass spectrometry. Direct structural modifications not only may affect protein-protein interactions, but can allow conformational switches to be constructed using single domain proteins. Using the NFAT regulatory domain as an example, we show these changes can not only modify the secondary structure of the protein locally but also globally alter protein tertiary structure, thus allowing phosphorylation to reset the switch.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在哺乳动物细胞中，蛋白质最初以20种不同氨基酸类型的异质聚合物表示。但是，蛋白质通常需要更多的亚基。通过共价翻译后修饰（例如糖基化，甲基化或核苷酸化）来实现这种更大的多样性。这些修饰可以通过扰动其能量景观并改变其功能来导致蛋白质的构象变化。 在本文中，我们解决了最重要的可逆修饰形式之一的能量和结构后果：磷酸化。在磷酸肽中，丝氨酸，苏氨酸，酪氨酸和组氨酸的侧链极性氢可以被磷酸基团取代。磷酸化在信号转导调节中经常发生，并且由于质谱的进步，在整个基因组中越来越多地注意到。直接的结构修饰不仅可能影响蛋白质 - 蛋白质相互作用，而且可以允许使用单域蛋白质构建构象开关。以NFAT调节结构域为例，我们表明这些变化不仅可以修改局部蛋白质的二级结构，而且还可以改变蛋白质的第三纪结构，从而允许磷酸化重置开关。