Prediction of the Structures of Protein Complexes

蛋白质复合物结构的预测

基本信息

批准号：
10693822
负责人：
JEFFREY J GRAY
金额：
$ 79.12万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10693822
关键词：
Antibodies Antigens Area Binding Binding Proteins Biological Biological Process Biophysics Carbohydrates Collaborations Communicable Diseases Complex Computer Models Computer software Computing Methodologies Development Diagnostic Disease Docking Engineering Health Human Immunology Individual Industry Infrastructure International Intervention Lead Malignant Neoplasms Methods Modeling Molecular Molecular Conformation Molecular Structure National Institute of General Medical Sciences Pharmaceutical Preparations Polysaccharides Post-Translational Protein Processing Protein Conformation Protein Engineering Proteins Resolution Route Scheme Scientist Software Design Structure Teaching Materials Testing Tissue Engineering Training Work design drug mechanism innovation insight operation polypeptide protein complex protein function protein phosphatase inhibitor-2 protein protein interaction protein structure prediction scripting interface synergism three dimensional structure tool web interface web server

项目摘要

Prediction of the Structures of Protein Complexes Jeffrey J. Gray, NIGMS R35 (MIRA) PROJECT SUMMARY Protein interactions are involved in nearly all biological processes in human health and diseases, and protein complex structures can reveal biological mechanisms and suggest intervention strategies. Computational modeling provides an alternative route to elucidate structures. Modeling also tests our understanding of molecular biophysics and allows us to engineer molecules based on their structures. My lab is a pioneer in developing computational methods to predict and design protein–protein interfaces and in applying those methods broadly, from immunology and cancer to infectious disease and tissue engineering. Our central focus is on protein–protein docking, that is, predicting the structure of a complex from the components (individual polypeptides or domains). A longstanding challenge in docking is correctly capturing protein conformational change, and we lead development of innovative search strategies and rapid scoring schemes to close this gap. Another focus area is the modeling and design of antibodies, directly supporting drug and diagnostic agent development and optimization. We predict high-resolution antibody structures from sequence, dock those models to antigens, and design antibodies to target specific antigens. Several protein modifications are important to consider when modeling interfaces. The emergence of powerful experimental methods for characterizing glycans has prompted us to expand our tools to model carbohydrates including docking methods and focused studies on glycotransferases. All our methods are embedded in the Rosetta software platform, which is used by tens of thousands of academic and industry scientists worldwide. The utility of our work is evidenced by the high demand for our prediction and design web server, scripting platform, and teaching materials. By leading the technical and scientific testing operations for the Rosetta Commons, my lab powers the synergies to combine Rosetta's powerful biomolecular prediction and design methods across this international collaboration.

蛋白质复合物结构的预测杰弗里·J·格雷，NIGMS R35 (MIRA) 项目概要蛋白质相互作用涉及人类健康和疾病的几乎所有生物过程，蛋白质复杂的结构可以揭示生物学机制并提出干预策略。建模提供了一种阐明结构的替代途径，建模也测试了我们对结构的理解。分子生物物理学，使我们能够根据分子的结构来设计分子，我的实验室是这方面的先驱。开发计算方法来预测和设计蛋白质-蛋白质界面并应用这些方法广泛的方法，从免疫学和癌症到传染病和组织工程。是关于蛋白质-蛋白质对接，即从成分（个体）预测复合物的结构对接中的一个长期挑战是正确捕获蛋白质构象。变化，我们领导创新搜索策略和快速评分方案的开发，以缩小这一差距。另一个重点领域是抗体的建模和设计，直接支持药物和诊断剂我们根据序列预测高分辨率抗体结构，并将其对接。抗原模型并设计针对特定抗原的抗体。一些蛋白质修饰很重要。接口建模时需要考虑的强大实验方法的出现。聚糖使我们能够扩展我们的工具来模拟碳水化合物，包括提示对接方法和重点我们所有的方法都嵌入在 Rosetta 软件平台中，供以下公司使用。全球数以万计的学术和工业科学家的成果证明了我们工作的实用性。对我们的预测和设计网络服务器、脚本平台和教材的需求罗塞塔共享区的技术和科学测试操作，我的实验室提供协同作用以结合起来 Rosetta 在这次国际合作中提供了强大的生物分子预测和设计方法。