Postdoctoral: Physical Geometric Algorithms and Systems for High-Throughput NMR Structural Biology

[0102710] donald， bruce artmouth学院ecise实验计算机科学博士后助理：用于高通量核磁共振的物理几何算法和系统虽然自动化正在彻底改变生物学的许多方面，但三维蛋白质结构的确定仍然是一项昂贵的任务。通过核磁共振（NMR）光谱测定蛋白质结构的传统自动化和半自动方法需要数十次实验和数月的光谱仪时间，因此不适合高通量自动化。研究建议是开发算法和系统，仅从几个关键的核磁共振光谱来确定蛋白质结构。该系统将使用类似于物理几何算法、模式识别和机器视觉、信号处理和机器人的算法，以分析光谱，将光谱峰分配给原子相互作用，计算二级结构，并估计全局折叠。以前开发的软件JIGSAW用编码氨基酸残基之间潜在相互作用的图形表示核磁共振数据。JIGSAW应用图算法来寻找编码二级蛋白质结构的子图。该博士后研究员将在JIGSAW的基础上，协助完成以下工作：1)整合三维输入光谱中的几何和相关性的自动分析；2)在随机图形式中证明结果的正确性、完整性和复杂性；3)将JIGSAW扩展到更大的蛋白质；4)利用远程相互作用来估计三维蛋白质结构。

0102710Donald, BruceDartmouth CollegeCISE Postdoctoral Associates in Experimental Computer Science: Physical Geometric Algorithms and Systems for High-Throughput NMRWhile automation is revolutionizing many aspects of biology, the determination of three-dimensional protein structure remains an expensive task. Traditional automated and semiautomated approaches to protein structure determination through nuclear magnetic resonance (NMR) spectroscopy require dozens of experiments and months of spectrometer time, making them unsuitable for high-throughput automation. The research proposed is to develop algorithms and systems for determining protein structure from only a few key NMR spectra. The system will use algorithms similar to and adapted from physical geometric algorithms, pattern recognition and machine vision, signal processing, and robotics, in order to analyze spectra, assign spectral peaks to atom interactions, compute secondary structure, and estimate the global fold. Previously developed software, JIGSAW, represents NMR data with graphs encoding potential interactions between amino acid residues. JIGSAW applies graph algorithms to find subgraphs encoding the secondary protein structure. The postdoctoral research associate will build on the insights of JIGSAW by assisting to 1) integrate automated analysis of geometry and correlations in three-dimensional input spectra, 2) prove correctness, completeness, and complexity results within a random graph formalism, 3) extend JIGSAW to larger proteins, and 4) utilize long-range interactions in order to estimate three-dimensional protein structure.