We find that a conserved mutation residue Glu to residue Asp （E303D）, which both have the same polar and charged properties, makes Kit2.1 protein lose its function. To understand the mechanism, we identify three int...We find that a conserved mutation residue Glu to residue Asp （E303D）, which both have the same polar and charged properties, makes Kit2.1 protein lose its function. To understand the mechanism, we identify three interactions which control the conformation change and maintain the function of the Kit2.1 protein by combining homology modeling and molecular dynamics with targeted molecular dynamics. We find that the E303D mutation weakens these interactions and results in the loss of the related function. Our data indicate that not only the amino residues but also the interactions determine the function of proteins.展开更多
A counter-streaming flow system is a test-bed to investigate the astrophysical collisionless shock（CS） formation in the laboratory. Electrostatic/electromagnetic instabilities, competitively growing in the system an...A counter-streaming flow system is a test-bed to investigate the astrophysical collisionless shock（CS） formation in the laboratory. Electrostatic/electromagnetic instabilities, competitively growing in the system and exciting the CS formation, are sensitive to the flows parameters. One of the most important parameters is the velocity, determining what kind of instability contributes to the shock formation. Here we successfully measure the evolution of the counter-streaming flows within one shot using a multi-pulses imaging diagnostic technique. With the technique, the average velocity of the high-density-part（ne ≥ 8–9 × 10^19cm^-3） of the flow is directly measured to be of ～ 10^6cm/s between 7 ns and 17 ns.Meanwhile, the average velocity of the low-density-part（ne ≤ 2 × 10^19cm^-3） can be estimated as ～ 10^7cm/s. The experimental results show that a collisionless shock is formed during the low-density-part of the flow interacting with each other.展开更多
Magnetic exchange interactions(MEIs) define networks of coupled magnetic moments and lead to a surprisingly rich variety of their magnetic properties. Typically MEIs can be estimated by fitting experimental results.Un...Magnetic exchange interactions(MEIs) define networks of coupled magnetic moments and lead to a surprisingly rich variety of their magnetic properties. Typically MEIs can be estimated by fitting experimental results.Unfortunately, how many MEIs need to be included in the fitting process for a material is unclear a priori,which limits the results obtained by these conventional methods. Based on linear spin-wave theory but without performing matrix diagonalization, we show that for a general quadratic spin Hamiltonian, there is a simple relation between the Fourier transform of MEIs and the sum of square of magnon energies(SSME). We further show that according to the real-space distance range within which MEIs are considered relevant, one can obtain the corresponding relationships between SSME in momentum space. By directly utilizing these characteristics and the experimental magnon energies at only a few high-symmetry k points in the Brillouin zone, one can obtain strong constraints about the range of exchange path beyond which MEIs can be safely neglected. Our methodology is also generally applicable for other Hamiltonian with quadratic Fermi or Boson operators.展开更多
Protein-protein interactions and enzyme-catalyzed reactions are the fundamental processes in life,and the quantification and manipulation,kinetics determination,and ether activation or inhibition of these processes ar...Protein-protein interactions and enzyme-catalyzed reactions are the fundamental processes in life,and the quantification and manipulation,kinetics determination,and ether activation or inhibition of these processes are critical for fully understanding physiological processes and discovering new medicine.Various methodologies and technologies have been developed to determine the parameters of these biological and medical processes.However,due to the extreme complexity of these processes,current methods and technologies can only determine one or a few parameters.The recent development of quantitative Forster resonance energy transfer(qFRET)methodology combined with technology aims to establish a high-throughput assay platform to determine protein interaction affinity,enzymatic kinetics,high-throughput screening,and pharmacological parameters using one assay platform.The FRET assay is widely used in biological and biomedical research in vitro and in vivo and provides high-sensitivity measurement in real time.Extensive efforts have been made to develop the FRET assay into a quantitative assay to determine protein-protein interaction affinity and enzymatic kinetics in the past.However,the progress has been challenging due to complicated FRET signal analysis and translational hurdles.The recent qFRET analysis utilizes cross-wavelength correlation coefficiency to dissect the sensitized FRET signal from the total fluorescence signal,which then is used for various biochemical and pharmacological parameter determination,such as K_(D),K_(cat),K_(M),K_(i),IC_(50),and product inhibition kinetics parameters.The qFRET-based biochemical and pharmacological parameter assays and qFRET-based screenings are conducted in 384-well plates in a high-throughput assay mode.Therefore,the qFRET assay platform can provide a universal high-throughput assay platform for future large-scale protein characterizations and therapeutics development.展开更多
基金Supported by the National Natural Science Foundation of China under Grant Nos 11247010,11175055,11475053 and 11347017the Natural Science Foundation of Hebei Province under Grant Nos C2012202079 and C201400305
文摘We find that a conserved mutation residue Glu to residue Asp （E303D）, which both have the same polar and charged properties, makes Kit2.1 protein lose its function. To understand the mechanism, we identify three interactions which control the conformation change and maintain the function of the Kit2.1 protein by combining homology modeling and molecular dynamics with targeted molecular dynamics. We find that the E303D mutation weakens these interactions and results in the loss of the related function. Our data indicate that not only the amino residues but also the interactions determine the function of proteins.
基金Project supported by the National Basic Research Program of China(Grant No.2013 CBA01501/3)the National Natural Science Foundation of China(Grant Nos.11503041,11135012,11375262,11573040,11574390,and 11220101002)China Postdoctoral Science Foundation(Grant No.2015M571124)
文摘A counter-streaming flow system is a test-bed to investigate the astrophysical collisionless shock（CS） formation in the laboratory. Electrostatic/electromagnetic instabilities, competitively growing in the system and exciting the CS formation, are sensitive to the flows parameters. One of the most important parameters is the velocity, determining what kind of instability contributes to the shock formation. Here we successfully measure the evolution of the counter-streaming flows within one shot using a multi-pulses imaging diagnostic technique. With the technique, the average velocity of the high-density-part（ne ≥ 8–9 × 10^19cm^-3） of the flow is directly measured to be of ～ 10^6cm/s between 7 ns and 17 ns.Meanwhile, the average velocity of the low-density-part（ne ≤ 2 × 10^19cm^-3） can be estimated as ～ 10^7cm/s. The experimental results show that a collisionless shock is formed during the low-density-part of the flow interacting with each other.
基金Supported by the National Natural Science Foundation of China (Grant Nos. 11834006, 12004170, and 12104215)the Natural Science Foundation of Jiangsu Province,China (Grant No. BK20200326)+1 种基金the Excellent Programme in Nanjing Universitythe support from the Tencent Foundation through the XPLORER PRIZE。
文摘Magnetic exchange interactions(MEIs) define networks of coupled magnetic moments and lead to a surprisingly rich variety of their magnetic properties. Typically MEIs can be estimated by fitting experimental results.Unfortunately, how many MEIs need to be included in the fitting process for a material is unclear a priori,which limits the results obtained by these conventional methods. Based on linear spin-wave theory but without performing matrix diagonalization, we show that for a general quadratic spin Hamiltonian, there is a simple relation between the Fourier transform of MEIs and the sum of square of magnon energies(SSME). We further show that according to the real-space distance range within which MEIs are considered relevant, one can obtain the corresponding relationships between SSME in momentum space. By directly utilizing these characteristics and the experimental magnon energies at only a few high-symmetry k points in the Brillouin zone, one can obtain strong constraints about the range of exchange path beyond which MEIs can be safely neglected. Our methodology is also generally applicable for other Hamiltonian with quadratic Fermi or Boson operators.
基金supported by the National Institutes of Health Grant AI076504,the UCR Academic Senate Grant,and the Attaisina gift grant.
文摘Protein-protein interactions and enzyme-catalyzed reactions are the fundamental processes in life,and the quantification and manipulation,kinetics determination,and ether activation or inhibition of these processes are critical for fully understanding physiological processes and discovering new medicine.Various methodologies and technologies have been developed to determine the parameters of these biological and medical processes.However,due to the extreme complexity of these processes,current methods and technologies can only determine one or a few parameters.The recent development of quantitative Forster resonance energy transfer(qFRET)methodology combined with technology aims to establish a high-throughput assay platform to determine protein interaction affinity,enzymatic kinetics,high-throughput screening,and pharmacological parameters using one assay platform.The FRET assay is widely used in biological and biomedical research in vitro and in vivo and provides high-sensitivity measurement in real time.Extensive efforts have been made to develop the FRET assay into a quantitative assay to determine protein-protein interaction affinity and enzymatic kinetics in the past.However,the progress has been challenging due to complicated FRET signal analysis and translational hurdles.The recent qFRET analysis utilizes cross-wavelength correlation coefficiency to dissect the sensitized FRET signal from the total fluorescence signal,which then is used for various biochemical and pharmacological parameter determination,such as K_(D),K_(cat),K_(M),K_(i),IC_(50),and product inhibition kinetics parameters.The qFRET-based biochemical and pharmacological parameter assays and qFRET-based screenings are conducted in 384-well plates in a high-throughput assay mode.Therefore,the qFRET assay platform can provide a universal high-throughput assay platform for future large-scale protein characterizations and therapeutics development.
