Conceptual Aspects of the Protein Folding Problem

蛋白质折叠问题的概念方面

• 批准号: 8471706
• 负责人: Peter Guy Wolynes
• 金额: $ 28.52万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8471706
• 关键词: Accounting; Affect; Algorithms; Biological; Cells; Cereals; Collaborations; Computer Simulation; Coupled; Coupling; Cystic Fibrosis; Data; Defect; Disease; Drug Design; Drug Targeting; Equilibrium; Evolution; Free Energy; Frustration; Genome; Genomics; Globular Protein Foldings; Health; In Vitro; Kinetics; Lead; Ligand Binding; Mediating; Membrane; Membrane Proteins; Modeling; Motion; Mutation; Non-Insulin-Dependent Diabetes Mellitus; Oncogenic; Organism; Phase; Phosphotransferases; Post-Translational Protein Processing; Principal Investigator; Process; Protein Dynamics; Protein Region; Proteins; Role; Structure; Surveys; Techniques; Translating; Transport Process; Water; Work; base; conformational conversion; globular protein; improved; in vivo; programs; protein folding; protein misfolding; protein structure; simulation; theories; tool

DESCRIPTION (provided by applicant): The proposed work develops further the statistical energy landscape approach to protein folding dynamics and structural prediction. The specific aims are: 1) to elucidate coupling of the folding and functional energy landscapes of allosteric proteins, concentrating on the role of local frustration 2) to elucidate the mechanism of in vitro and in vivo folding of membrane proteins and to improve our ability to predict their structure. Energy landscape theory provides mathematical techniques for characterizing in probabilistic terms the energies of the ensembles of partially folded protein configurations and the dynamics of interconverting between them. We will use analytical and computer simulation approaches that will provide quantitative estimates for the role of minimally frustrated networks of interactions in guiding the protein to its native state and the role that frustration has in impeding that flow. Allosteric proteins are predicted to positively use frustration to sculpt the functional landscape. Mutation in allosteric proteins such as kinases can cause a protein to be oncogenic. Errors in the folding of membrane proteins can lead specifically to diseases such as cystic fibrosis. Advances in understanding the landscape of membrane protein can help predict their structure an important step in designing drugs. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page

描述（由申请人提供）：拟议的工作进一步开发了蛋白质折叠动力学和结构预测的统计能量景观方法。具体目标是：1）阐明变构蛋白折叠和功能能量景观的耦合，重点关注局部挫败的作用2）阐明膜蛋白体外和体内折叠的机制，并提高我们预测其结构的能力。能量景观理论提供了用概率术语表征部分折叠蛋白质构型整体的能量以及它们之间相互转换的动力学的数学技术。我们将使用分析和计算机模拟方法，为最小受挫相互作用网络在引导蛋白质达到其天然状态方面的作用以及受挫在阻碍这种流动中的作用提供定量估计。预计变构蛋白将积极利用挫折来塑造功能景观。激酶等变构蛋白的突变可导致蛋白质致癌。膜蛋白折叠错误可能会导致囊性纤维化等疾病。了解膜蛋白景观的进展可以帮助预测其结构，这是设计药物的重要一步。 PHS 398/2590（修订版 11/07） 页面延续 格式页面