Optimization of Stuctures and Networks of Proteins

蛋白质结构和网络的优化

• 批准号: 7466765
• 负责人: Ron Elber
• 金额: $ 30.52万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7466765
• 关键词: Address; Algorithms; Area; Bioinformatics; Biological; Categories; Class; Code; Collaborations; Communities; Complex; Computational Biology; Computer software; Docking; Drug Design; Electrostatics; Employee Strikes; Equation; Evaluation; Evolution; Facility Construction Funding Category; Future; Gene Duplication; Goals; Grant; Graph; Homology Modeling; Humulus; Hydrogen Bonding; Hydrophobicity; Learning; Machine Learning; Martes zibellina; Modeling; Molecular Conformation; Output; Pathway interactions; Pattern; Pediatric Hospitals; Performance; Pharmaceutical Preparations; Physics; Point Mutation; Process; Progress Reports; Protein Dynamics; Proteins; Public Health; Research; Resolution; Roentgen Rays; Score; Sequence Analysis; Services; Signal Transduction; Solvents; Structure; Surface; Testing; Torsion; University Hospitals; Work; base; design; desire; experience; improved; insertion/deletion mutation; molecular dynamics; novel; programs; protein function; protein protein interaction; protein structure; protein structure prediction; research study; simulation; tool

DESCRIPTION (provided by applicant): This application has three major aims that exploit the use of mathematical programming tools for biophysically motivated problems. The first goal is the refinement of protein structures that are obtained from homology. Structures based on homology are rarely of atomic resolution; a resolution which is necessary for detailed modeling of protein function, and for the design of drug molecules. Based on mathematical programming approach a new class of energy functions, suitable for the refinement problem, will be designed. The second goal is to investigate a new type of network; the network of sequence flow between protein structures. We examine the process in which new sequences, generated by point mutations, remain in the current fold, or switch to other stable structures (we exclude sequences with no stable fold). The adjustments to the structure are accepted or rejected based on stability criterion. The net. work defines a master equation which makes it possible to investigate past (ancient) folds, and future structures that serve as attractors. The third aim examines the network of protein-protein (physical) interactions and will be examined with bioinformatics and biophysical approaches. Comparison will be made between the network of sequence flow and the network of protein-protein interactions to better understand the evolution of biological mechanisms and recognition. PUBLIC HEALTH RELEVANCE The design of new algorithms to predict protein structures and protein-protein interactions is likely to help with the design of new drug molecules.

描述（由申请人提供）：该应用程序有三个主要目的，即利用数学规划工具来解决生物物理问题。第一个目标是改进从同源性中获得的蛋白质结构。基于同源性的结构很少具有原子分辨率；这种分辨率对于蛋白质功能的详细建模和药物分子的设计是必要的。基于数学规划的方法，将设计一类新的能量函数，适合于细化问题。第二个目标是研究一种新型的网络；蛋白质结构之间的序列流动网络。我们研究了由点突变产生的新序列保持在当前褶皱中或切换到其他稳定结构的过程（我们排除了没有稳定褶皱的序列）。根据稳定性判据对结构的调整进行接受或拒绝。净。工作定义了一个主方程，使研究过去（古代）褶皱和未来作为吸引子的结构成为可能。第三个目标是检查蛋白质-蛋白质（物理）相互作用的网络，并将与生物信息学和生物物理方法进行检查。将序列流网络与蛋白质-蛋白质相互作用网络进行比较，以更好地了解生物机制和识别的进化。设计新的算法来预测蛋白质结构和蛋白质-蛋白质相互作用可能有助于设计新的药物分子。