Dynamics and Mechanism of Water-Protein Interactions

水-蛋白质相互作用的动力学和机制

基本信息

批准号：
8725688
负责人：
DONGPING ZHONG
金额：
$ 28.98万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8725688
关键词：
Active Sites Address Amino Acids Architecture Benchmarking Binding Binding Sites Biological Process Catalysis Chemical Structure Chemicals Complex Coupled Coupling DNA DNA-Directed DNA Polymerase Data Docking Drug Design Enzymes Evolution Future Goals Heterogeneity Hydration status Investigation Isotopes Knowledge Lasers Lead Life Maps Mediation Membrane Proteins Methodology Methods Modeling Molecular Motion Mutation Nature Neurodegenerative Disorders Optics Prevention Property Protein Dynamics Protein Engineering Proteins Relaxation Research Resolution Role Scanning Science Series Site-Directed Mutagenesis Spectrum Analysis Structural Protein Structure Surface System Temperature Time Tryptophan Water biological systems flexibility globular protein improved insight interfacial molecular dynamics molecular recognition mutant novel practical application protein aggregation protein protein interaction protein structure simulation

项目摘要

DESCRIPTION (provided by applicant): Protein hydration is a long-standing and unresolved problem in protein science and water-protein interactions/dynamics are essential to a protein's structure, dynamics and function. The elucidation of such coupling motions at the molecular level not only has fundamental significance in understanding protein stability and flexibility, folding, misfolding and aggregation, recognition and binding, and enzyme catalysis, but also has a significant impact on practical applications such as drug design. Various methods and strategies have been used to characterize water motions around proteins, but such studies have been challenging and difficult because the dynamics are ultrafast and heterogeneous. A general molecular picture has not been obtained yet. We have recently developed a methodology by integrating state-of-the-art femtosecond laser spectroscopy and site-directed mutagenesis and have reached femtosecond temporal resolution and single-residue spatial resolution. Using intrinsic amino acid tryptophan as a local optical probe, we have recently mapped out the global water motions around an a-helical globular protein with unprecedented details. In this proposal, we will systematically characterize water motions around small structural motifs, on surfaces of ¿-sheet globular proteins, and at interfaces of protein-DNA complexes. Specifically, Aim 1 is to elucidate the hydration dynamics evolution by systematic characterization of water motions from an a-helix, to a ¿-hairpin, to a small cage, and to a mini-protein. With the fundamental understanding of water motions around these elemental structure units, in Aim 2 we extend to characterize the global surface hydration dynamics around two ¿-sheet globular proteins. Combined with recently characterized water dynamics around the a-helical globular protein, we hope that such systematic comparisons will reveal the different dynamic nature of water motions around different protein architectures with different size, rigidity, chemical identity. Finally, in Aim 3, we investigate the interfacial hydration dynamics by systematic characterization of water motions at the interfaces of two protein-DNA complexes to address the dynamic role of water motions in mediation of protein-DNA recognition. The new knowledge obtained from these systematic investigations is fundamental to a wide variety of biological processes and also significant to a series of practical applications.

描述（由申请人证明）：蛋白质水合是蛋白质科学和蛋白质IC的长期且未解决的问题，对于蛋白质的结构，动力学和功能是必不可少的。蛋白质和柔韧性，折叠，折叠和聚集，酶催化，但对诸如药物设计等实际应用有显着影响已获得。围绕具有未经预剖的细节的A螺旋蛋白的运动。 - 在蛋白质-DNA复合物的界面上，球形蛋白质的蛋白质。 - 海上，对围绕游戏的结构单位的水运动的基本理解倾向 - 球状蛋白质与近来的水动力学在A螺旋状蛋白蛋白蛋白周围的蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质蛋白质的蛋白质蛋白质蛋白质蛋白质蛋白质的蛋白质蛋白质蛋白质蛋白质的蛋白质蛋白质蛋白质蛋白质的蛋白质蛋白质蛋白质蛋白质的蛋白质蛋白质蛋白质蛋白质蛋白质的蛋白质蛋白质蛋白质的蛋白质蛋白质蛋白质蛋白质的蛋白质蛋白质蛋白质的蛋白质较大DNA Complyses Oaddress的动态识别水的动态作用。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Quenching Dynamics of Ultraviolet-Light Perception by UVR8 Photoreceptor.

DOI：
10.1021/jz402396k
发表时间：
2014-01-02
期刊：
The journal of physical chemistry letters
影响因子：
0
作者：
Liu Z;Li X;Zhong FW;Li J;Wang L;Shi Y;Zhong D
通讯作者：
Zhong D

Ultrafast water dynamics at the interface of the polymerase-DNA binding complex.

DOI：
10.1021/bi500810a
发表时间：
2014-08-26
期刊：
BIOCHEMISTRY
影响因子：
2.9
作者：
Yang, Yi;Qin, Yangzhong;Ding, Qing;Bakhtina, Marina;Wang, Lijuan;Tsai, Ming-Daw;Zhong, Dongping
通讯作者：
Zhong, Dongping

Direct probing of solvent accessibility and mobility at the binding interface of polymerase (Dpo4)-DNA complex.