Collapse versus aggregation of proteins

蛋白质的塌陷与聚集

• 批准号: 1152876
• 负责人: B. Montgomery Pettitt
• 金额: $ 39万
• 依托单位: University of Texas Medical Branch at Galveston
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1152876&HistoricalAwards=false
• 关键词: Collapse; versus; aggregation; proteins

In this award from the Chemistry of Life Processes Program in the Chemistry Division, Dr. B. Montgomery Pettitt, from the University of Texas Medical Branch, Galveston, seeks to understand, through computational approaches, the role of the solubility of the backbone and side chains in folding and recognition in peptides and proteins.The mechanisms governing recognition between proteins and the transition of proteins from their unfolded state to their native state in cells still remain as elusive fundamental questions. Recent experiments studying the interactions between cellular osmolytes and proteins have challenged the prevailing paradigm of the protein folding mechanism. Interpretation of those experiments holds that the backbone solubility difference in osmolyte is a dominant driving force rather than just the sidechains. Recent theoretical efforts to date have not resolved the issue. Dr. Pettitt's goals are to computationally test hypotheses concerning the magnitude of the nonideal backbone solubility in comparison to side chain solvation as driving forces in protein folding. His group will use glycine oligomers as models for the protein backbone and alanine oligomers as small fast folders to understand side chain effects in quantitative comparison to backbone.This research effort aims to resolve a critical issue concerning the chemical driving force for all protein folding. This goal has many far reaching societal benefits and is generally important for the fields of protein engineering and biotechnology. As such it will provide numerous interdisciplinary opportunities for the inclusion of women and underrepresented groups in the project. All participants will be encouraged to attend both national and local meetings of relevance. Dr. Pettitt is well positioned to recruit minority and female students and post-doctorates to participate in this project. His group works with the Rice/Houston Alliance for Graduate Education and the Professoriate and the Houston-Louis Stokes Alliance for Minority Participation, which includes the University of Houston-Downtown, Texas State University-San Marcos, and Texas Southern University, among others.

来自加尔维斯顿德克萨斯大学医学分校的B.Montgomery Pettit博士在化学部生命过程化学项目的这一奖项中，试图通过计算方法了解主链和侧链的溶解性在多肽和蛋白质折叠和识别中的作用。控制蛋白质之间识别的机制以及蛋白质在细胞中从未折叠状态到自然状态的转变仍然是难以捉摸的基本问题。最近研究细胞渗透分子和蛋白质相互作用的实验对蛋白质折叠机制的主流范式提出了挑战。对这些实验的解释认为，骨架在渗透沸石中的溶解度差异是主导驱动力，而不仅仅是侧链。到目前为止，最近的理论努力还没有解决这个问题。派提特博士的目标是通过计算测试与侧链溶剂化作为蛋白质折叠驱动力的非理想主链溶解度的大小相关的假设。他的团队将使用甘氨酸低聚物作为蛋白质骨架的模型，使用丙氨酸低聚物作为小的快速文件夹，以了解与骨架的定量比较中的侧链效应。这项研究旨在解决关于所有蛋白质折叠的化学驱动力的关键问题。这一目标具有许多深远的社会效益，通常对蛋白质工程和生物技术领域很重要。因此，它将为将妇女和代表性不足的群体纳入该项目提供许多跨学科的机会。将鼓励所有与会者参加有意义的国家和地方会议。佩蒂特博士很有能力招募少数族裔和女性学生以及博士后参与这一项目。他的团队与莱斯/休斯顿研究生教育和教授联盟以及休斯顿-路易斯·斯托克斯少数群体参与联盟合作，该联盟包括休斯顿市中心大学、德克萨斯州立大学圣马科斯分校和德克萨斯南方大学等。