ULTRAFAST OPTICAL PROCESSES LABORATORY

超快光学工艺实验室

基本信息

批准号：
9476438
负责人：
FENG GAI
金额：
$ 24.31万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9476438
关键词：
Amyloid Amyloid Proteins Anti-HIV Agents Automobile Driving Azides Biochemistry Biological Biology Biomedical Research Biophysics Blood coagulation Cells Complex Coupling Cyclotrons Databases Detection Development Dimensions Drug Design Ensure Equilibrium Evolution Fluorescence Frequencies Future Goals Grant HIV Histidine Influenza A virus Isotopes Kinetics Laboratories Lasers Learning Measures Medicine Methodology Methods Microscopy Modeling Molecular Conformation Nitriles Optics Oxygen Pennsylvania Phase Phosphotransferases Photons Physiologic pulse Process Property Proteins Protons RNA-Directed DNA Polymerase Research Research Project Grants Resolution Resource Development Resources Roentgen Rays Science Services Signal Transduction Source Spectrum Analysis Structural Protein Structure Technology Testing Time Training Universities Variant Vertebral column Water Work biological research chemical bond experimental study free-electron laser human disease improved infrared spectroscopy inhibitor/antagonist instrumentation macromolecule new technology novel novel strategies peptide structure protein structure research and development response scale up simulation success three dimensional structure two-dimensional water channel

项目摘要

The Ultrafast Laser Resource at the University of Pennsylvania is founding the technoogies for multidimensional infrared spectroscopy in biological and biomedical research including drug design. The components of the laboratory are an integrated multifaceted attack on advancing two dimensional infrared methods. Each TR&D is dynamically evolving at the cutting edge of infrared technology, they are mutually supportive. The utility of 2D IR in biomedical applications is increasing substantially. Just within the last year a protein structure has been determined by 2D IR. TR&D's #1 focuses on phototriggered states, the technology combines optical and infrared methods to obtain 2D IR structural-time dependent information during nonequilibrium dynamical processes. The TR&D #2 concerns dual frequency 2D IR which combines into a two dimensional spectrum the excitation of two modes having widely separated frequencies of proteins and proton channels. TR&D#3 involves a specialization on structure determination, to build on previous studies using 2D IR, by improvements in the methodology that are specifically geared towards the equilibrium dynamics of structures of proteins on time scales that have not been achieved by other structural methods. Six DBF's are included: (1)The M2 proton channel of the Influenza A virus: properties of channel water (W.F. DeGrado, UCSF).(2)The structure and dynamics of amyloid A40 fibrils and their formation kinetics (P. Abelson, Upend) (3) Phototriggering of conformational change (A.B. Smith, Upend)) (4) Pushing the Structural Resolution Limit of Linear and Nonlinear Infrared Spectroscopies (F. Gai, Upend) (5) Radical pair dynamics by optically triggered - IR probe spectroscopy (S. Vinogradov, Upend) (6) Spectroscopy and dynamics of HlV-1 RT/inhibitor complexes probed by 2D IR methods and MD simulations (E. Arnold, Rutgers). The proposal also includes seven Collaborative and Service projects on (1) Nitrile and Azide probes (Brewer) (2) Protonated histidines (Londergan) (3) Amyloid fluorescence (Petersson)(4) Blood coagulation (Knshnaswamy) (5) Kinases models (Sarkar)(6)Amyloid kinetics (Dai) (7) Oxygen microscopy (Vinogradov), The Resource provides training for users, and the work is widely disseminated.

宾夕法尼亚大学的超快激光资源正在为生物和生物医学研究（包括药物设计）建立多维红外光谱技术。该实验室的组成部分是对先进二维红外方法的综合多方面攻击。每个 TR&D 都在红外技术的前沿动态发展，它们是相互支持的。二维红外在生物医学应用中的效用正在大幅增加。就在去年，通过二维红外确定了蛋白质结构。 TR&D 的#1 专注于光触发态，该技术结合了光学和红外方法，在非平衡动态过程中获取二维红外结构时间相关信息。 TR&D #2 涉及双频 2D IR，它将具有广泛分离的蛋白质和质子通道频率的两种模式的激发组合成二维光谱。 TR&D#3 涉及结构测定的专业化，以先前使用 2D IR 进行的研究为基础，通过改进方法，专门针对时间尺度上蛋白质结构的平衡动力学，这是其他结构方法无法实现的。其中包括 6 个 DBF：(1) 甲型流感病毒的 M2 质子通道：通道水的特性（W.F. DeGrado，UCSF）。(2) 淀粉样蛋白 A40 原纤维的结构和动力学及其形成动力学（P. Abelson，Upend） ) (3) 构象变化的光触发 (A.B. Smith, Upend)) (4) 突破线性和线性的结构分辨率极限非线性红外光谱 (F. Gai, Upend) (5) 通过光学触发的自由基对动力学 - 红外探针光谱 (S. Vinogradov, Upend) (6) 通过 2D IR 方法探测 HIV-1 RT/抑制剂复合物的光谱和动力学MD 模拟（E. Arnold，罗格斯大学）。该提案还包括七个合作和服务项目，涉及 (1) 腈和叠氮化物探针 (Brewer) (2) 质子化组氨酸 (Londergan) (3) 淀粉样蛋白荧光 (Petersson)(4) 凝血 (Knshnaswamy) (5) 激酶模型 ( Sarkar)(6)淀粉样蛋白动力学 (Dai) (7) 氧显微镜 (Vinogradov)，该资源提供培训用户，作品得到广泛传播。