There are rich emergent phase behaviors in non-equilibrium active systems.Flocking and clustering are two representative dynamic phases.The relationship between both the phases is still unclear.Herein,we numerically i...There are rich emergent phase behaviors in non-equilibrium active systems.Flocking and clustering are two representative dynamic phases.The relationship between both the phases is still unclear.Herein,we numerically investigate the evolution of flocking and clustering in a system consisting of self-propelled particles with active reorientation.We consider the interplay between flocking and clustering phases with different initial configurations,and observe a domain in steady state order parameter phase diagrams sensitive to the choice of initial configurations.Specifically,by tuning the initial degree of polar ordering,either a more ordered flocking or a disordered clustering state can be observed in the steady state.These results enlighten us to manipulate emergent behaviors and collective motions of an active system,and are qualitatively different from the emergence of a new bi-stable regime observed in aligned active particles due to an explicit attraction[New J.Phys.14073033(2012)].展开更多
CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 （1L8） molecules. This study combines homology modeling and molecular dynamics simulation methods to study t...CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 （1L8） molecules. This study combines homology modeling and molecular dynamics simulation methods to study the structure of CXCRI-IL8 complex. By using CXCR4-vMIP-II crystallography structure as the homologous template, CXCRI-IL8 complex structure was constructed, and then refined using all-atom molecular dynamics simulations. Through extensive simulations, CXCRI-IL8 binding poses were investigated in detail. Furthermore, the role of the N-terminal of CXCR1 receptor was studied by comparing four complex models differing in the N-terminal sequences. The results indicate that the receptor N-terminal affects the binding of IL8 significantly. With a shorter N-terminal domain, the binding of IL8 to CXCR1 becomes unstable. The homology modeling and simulations also reveal the key receptor-ligand residues involved in the electrostatic interactions known to be vital for complex formation.展开更多
We study phase behaviors of mixtures comprising active particles with and without active reorientation by varying mixing ratios.We observe that the order parameter characterizing flocking in the steady state exhibits ...We study phase behaviors of mixtures comprising active particles with and without active reorientation by varying mixing ratios.We observe that the order parameter characterizing flocking in the steady state exhibits a linear decrease with an increase in mixing ratio.While the order parameter characterizing clustering in the steady state presents a sharp leap as the mixing ratio increases.Particularly,we obtain phase diagrams of flocking under different mixing ratios and observe that the domain corresponding to flocking experiences a contraction with the increase of mixing ratio.Simultaneously,the coordinates of the critical point on the phase boundary between the flocking and the disordered phase decay exponentially with the mixing ratio.展开更多
The CryoEM single particle structure determination method has recently received broad attention in the field of structural biology. The structures can be resolved to near-atomic resolutions after model reconstructions...The CryoEM single particle structure determination method has recently received broad attention in the field of structural biology. The structures can be resolved to near-atomic resolutions after model reconstructions from a large number of CryoEM images measuring molecules in different orientations. However, the determining factors for reconstructed map resolution need to be further explored. Here, we provide a theoretical framework in conjunction with numerical simulations to gauge the influence of several key factors to CryoEM map resolutions. If the projection image quality allows orientation assignment, then the number of measured projection images and the quality of each measurement(quantified using average signal-to-noise ratio) can be combined to a single factor, which is dominant to the resolution of reconstructed maps. Furthermore, the intrinsic thermal motion of molecules has significant effects on the resolution. These effects can be quantitatively summarized with an analytical formula that provides a theoretical guideline on structure resolutions for given experimental measurements.展开更多
The tunneling current in a graphene nanoribbon tunnel field effect transistor(GNR-TFET) has been quantum mechanically modeled. The tunneling current in the GNR-TFET was compared based on calculations of the Dirac-like...The tunneling current in a graphene nanoribbon tunnel field effect transistor(GNR-TFET) has been quantum mechanically modeled. The tunneling current in the GNR-TFET was compared based on calculations of the Dirac-like equation and Schrodinger’s equation. To calculate the electron transmittance, a numerical approach-namely the transfer matrix method(TMM)-was employed and the Launder formula was used to compute the tunneling current. The results suggest that the tunneling currents that were calculated using both equations have similar characteristics for the same parameters, even though they have different values. The tunneling currents that were calculated by applying the Dirac-like equation were lower than those calculated using Schrodinger’s equation.展开更多
Background:COVID-19 is an acute infection of the respiratory tract that emerged in late 2019.Currently identified methods for identifying the severe acute respiratory syndrome coronavirus 2 virus include methods that ...Background:COVID-19 is an acute infection of the respiratory tract that emerged in late 2019.Currently identified methods for identifying the severe acute respiratory syndrome coronavirus 2 virus include methods that detect the presence of the virus itself,such as reverse transcription PCR and isothermal amplification methods,and those that detect antibodies produced in response to the infection.Reverse transcription PCR and quantitative PCR are highly sensitive but have a narrow time window of sensitivity.Methods:We investigated a new method to detect the occurrence of severe acute respiratory syndrome coronavirus 2 by analyzing the early rise in leukocyte levels which has a characteristic set of ratios of leukocyte types which identify the viral pathogen and distinguish it from a number of others.We used the Albert Einstein Hospital,São Paulo data set and the Athena AI System to validate this method.Results:The sensitivity of the test is up to 98.67%prediction of positives from full blood count results.Conclusion:We have discovered an early test for SARS-CoV-2 which can be performed using a black-boxed AI to give high sensitivity prediction of COVID-19 infection.展开更多
Background:A novel coronavirus(the SARS-CoV-2)has been identified in January 2020 as the causal pathogen for COVID-19,a pandemic started near the end of 2019.The Angiotensin converting enzyme 2 protein(ACE2)utilized b...Background:A novel coronavirus(the SARS-CoV-2)has been identified in January 2020 as the causal pathogen for COVID-19,a pandemic started near the end of 2019.The Angiotensin converting enzyme 2 protein(ACE2)utilized by the SARS-CoV as a receptor was found to facilitate the infection of SARS-CoV-2,initiated by the binding of the spike protein to human ACE2.Methods:Using homology modeling and molecular dynamics(MD)simulation methods,we report here the detailed structure and dynamics of the ACE2 in complex with the receptor binding domain(RBD)of the SARS-CoV-2 spike protein.Results:The predicted model is highly consistent with the experimentally determined structures,validating the homology modeling results.Besides the binding interface reported in the crystal structures,novel binding poses are revealed from all-atom MD simulations.The simulation data are used to identify critical residues at the complex interface and provide more details about the interactions between the SARS-CoV-2 RBD and human ACE2.Conclusion:Simulations reveal that RBD binds to both open and closed state of ACE2.Two human ACE2 mutants and rat ACE2 are modeled to study the mutation effects on RBD binding to ACE2.The simulations show that the N-terminal helix and the K353 are very important for the tight binding of the complex,the mutants are found to alter the binding modes of the CoV2-RBD to ACE2.展开更多
X-ray Free Electron Lasers （XFELs） have advanced research in structure biology, by exploiting their ultra-short and bright X-ray pulses. The resulting ＂diffraction before destruction＂ experimental approach allows ...X-ray Free Electron Lasers （XFELs） have advanced research in structure biology, by exploiting their ultra-short and bright X-ray pulses. The resulting ＂diffraction before destruction＂ experimental approach allows data collection to outrun radiation damage, a crucial factor that has often limited resolution in the structure determination of biological molecules. Since the first hard X-ray laser （the Linac Coherent Light Source （LCLS） at SLAC） commenced operation in 2009, serial femtosecond crystallography （SFX） has rapidly matured into a method for the structural analysis of nano- and micro-crystals. At the same time, single particle structure determination by coherent diffractive imaging, with one particle （such as a virus） per shot, has been under intense development. In this review we describe these applications of X-ray lasers in structural biology, with a focus particularly on aspects of data analysis for the computational research community. We summarize the key problems in data analysis and model reconstruction, and provide perspectives on future research using computational methods.展开更多
Dear Editor,A disulfide bond that formed between the thiol groups of two spatially close cysteine residues is essential for protein folding, stability, and function (Creighton et al., 1995) (Fass, 2012). Driven by con...Dear Editor,A disulfide bond that formed between the thiol groups of two spatially close cysteine residues is essential for protein folding, stability, and function (Creighton et al., 1995) (Fass, 2012). Driven by conformational entropy, native disulfide bonds stabilize the conformation of protein molecules (Dill, 1990), while removal of native disulfides usually causes reduced stability of the target protein (Liu and Cowburn, 2016).展开更多
基金support from the Beijing Computational Science Research Centersupported by the National Natural Science Foundation of China(Grant Nos.U2230402,11975050,11735005,and 11904320)。
文摘There are rich emergent phase behaviors in non-equilibrium active systems.Flocking and clustering are two representative dynamic phases.The relationship between both the phases is still unclear.Herein,we numerically investigate the evolution of flocking and clustering in a system consisting of self-propelled particles with active reorientation.We consider the interplay between flocking and clustering phases with different initial configurations,and observe a domain in steady state order parameter phase diagrams sensitive to the choice of initial configurations.Specifically,by tuning the initial degree of polar ordering,either a more ordered flocking or a disordered clustering state can be observed in the steady state.These results enlighten us to manipulate emergent behaviors and collective motions of an active system,and are qualitatively different from the emergence of a new bi-stable regime observed in aligned active particles due to an explicit attraction[New J.Phys.14073033(2012)].
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11575021,U1530401,and U1430237)the National Research Foundation of Korea(Grant Nos.NRF-2017R1A2B2008483 and NRF-2016R1A6A3A04010213)
文摘CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 （1L8） molecules. This study combines homology modeling and molecular dynamics simulation methods to study the structure of CXCRI-IL8 complex. By using CXCR4-vMIP-II crystallography structure as the homologous template, CXCRI-IL8 complex structure was constructed, and then refined using all-atom molecular dynamics simulations. Through extensive simulations, CXCRI-IL8 binding poses were investigated in detail. Furthermore, the role of the N-terminal of CXCR1 receptor was studied by comparing four complex models differing in the N-terminal sequences. The results indicate that the receptor N-terminal affects the binding of IL8 significantly. With a shorter N-terminal domain, the binding of IL8 to CXCR1 becomes unstable. The homology modeling and simulations also reveal the key receptor-ligand residues involved in the electrostatic interactions known to be vital for complex formation.
基金supported by the National Natural Science Foundation of China(Grant No.11975050).
文摘We study phase behaviors of mixtures comprising active particles with and without active reorientation by varying mixing ratios.We observe that the order parameter characterizing flocking in the steady state exhibits a linear decrease with an increase in mixing ratio.While the order parameter characterizing clustering in the steady state presents a sharp leap as the mixing ratio increases.Particularly,we obtain phase diagrams of flocking under different mixing ratios and observe that the domain corresponding to flocking experiences a contraction with the increase of mixing ratio.Simultaneously,the coordinates of the critical point on the phase boundary between the flocking and the disordered phase decay exponentially with the mixing ratio.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11774011,11434001,U1530401,and U1430237)
文摘The CryoEM single particle structure determination method has recently received broad attention in the field of structural biology. The structures can be resolved to near-atomic resolutions after model reconstructions from a large number of CryoEM images measuring molecules in different orientations. However, the determining factors for reconstructed map resolution need to be further explored. Here, we provide a theoretical framework in conjunction with numerical simulations to gauge the influence of several key factors to CryoEM map resolutions. If the projection image quality allows orientation assignment, then the number of measured projection images and the quality of each measurement(quantified using average signal-to-noise ratio) can be combined to a single factor, which is dominant to the resolution of reconstructed maps. Furthermore, the intrinsic thermal motion of molecules has significant effects on the resolution. These effects can be quantitatively summarized with an analytical formula that provides a theoretical guideline on structure resolutions for given experimental measurements.
基金supported by Hibah Penelitian Berbasi Kompetensi 2018 RISTEKDIKTI Republic of Indonesia
文摘The tunneling current in a graphene nanoribbon tunnel field effect transistor(GNR-TFET) has been quantum mechanically modeled. The tunneling current in the GNR-TFET was compared based on calculations of the Dirac-like equation and Schrodinger’s equation. To calculate the electron transmittance, a numerical approach-namely the transfer matrix method(TMM)-was employed and the Launder formula was used to compute the tunneling current. The results suggest that the tunneling currents that were calculated using both equations have similar characteristics for the same parameters, even though they have different values. The tunneling currents that were calculated by applying the Dirac-like equation were lower than those calculated using Schrodinger’s equation.
文摘Background:COVID-19 is an acute infection of the respiratory tract that emerged in late 2019.Currently identified methods for identifying the severe acute respiratory syndrome coronavirus 2 virus include methods that detect the presence of the virus itself,such as reverse transcription PCR and isothermal amplification methods,and those that detect antibodies produced in response to the infection.Reverse transcription PCR and quantitative PCR are highly sensitive but have a narrow time window of sensitivity.Methods:We investigated a new method to detect the occurrence of severe acute respiratory syndrome coronavirus 2 by analyzing the early rise in leukocyte levels which has a characteristic set of ratios of leukocyte types which identify the viral pathogen and distinguish it from a number of others.We used the Albert Einstein Hospital,São Paulo data set and the Athena AI System to validate this method.Results:The sensitivity of the test is up to 98.67%prediction of positives from full blood count results.Conclusion:We have discovered an early test for SARS-CoV-2 which can be performed using a black-boxed AI to give high sensitivity prediction of COVID-19 infection.
基金supported by Bejjing Computational Science Research Center(CSRC)via a director discretionary grantThe authors acknowledge the Beijing Super Cloud Computing Center(BSCC)for providing HPC resources that have contributed to the researchThe rescarch is supported by the National Natural Science Foundation(No.U1930402).
文摘Background:A novel coronavirus(the SARS-CoV-2)has been identified in January 2020 as the causal pathogen for COVID-19,a pandemic started near the end of 2019.The Angiotensin converting enzyme 2 protein(ACE2)utilized by the SARS-CoV as a receptor was found to facilitate the infection of SARS-CoV-2,initiated by the binding of the spike protein to human ACE2.Methods:Using homology modeling and molecular dynamics(MD)simulation methods,we report here the detailed structure and dynamics of the ACE2 in complex with the receptor binding domain(RBD)of the SARS-CoV-2 spike protein.Results:The predicted model is highly consistent with the experimentally determined structures,validating the homology modeling results.Besides the binding interface reported in the crystal structures,novel binding poses are revealed from all-atom MD simulations.The simulation data are used to identify critical residues at the complex interface and provide more details about the interactions between the SARS-CoV-2 RBD and human ACE2.Conclusion:Simulations reveal that RBD binds to both open and closed state of ACE2.Two human ACE2 mutants and rat ACE2 are modeled to study the mutation effects on RBD binding to ACE2.The simulations show that the N-terminal helix and the K353 are very important for the tight binding of the complex,the mutants are found to alter the binding modes of the CoV2-RBD to ACE2.
文摘X-ray Free Electron Lasers （XFELs） have advanced research in structure biology, by exploiting their ultra-short and bright X-ray pulses. The resulting ＂diffraction before destruction＂ experimental approach allows data collection to outrun radiation damage, a crucial factor that has often limited resolution in the structure determination of biological molecules. Since the first hard X-ray laser （the Linac Coherent Light Source （LCLS） at SLAC） commenced operation in 2009, serial femtosecond crystallography （SFX） has rapidly matured into a method for the structural analysis of nano- and micro-crystals. At the same time, single particle structure determination by coherent diffractive imaging, with one particle （such as a virus） per shot, has been under intense development. In this review we describe these applications of X-ray lasers in structural biology, with a focus particularly on aspects of data analysis for the computational research community. We summarize the key problems in data analysis and model reconstruction, and provide perspectives on future research using computational methods.
基金This work was supported by the National Nature Science Foundationof China grant 31330019(Z.-J.L),11575021(H.L.),U1530401(H.L.),U1430237(H.L.)and 31500593(G.S.)the Ministry of Science and Technology of China grants 2014CB910400(Z.-J.L)and2015CB910104(Z.-J.L)This research work is supported by aTianhe-2JK computing time award at the Beijing Computational Research Center(CSRC).
文摘Dear Editor,A disulfide bond that formed between the thiol groups of two spatially close cysteine residues is essential for protein folding, stability, and function (Creighton et al., 1995) (Fass, 2012). Driven by conformational entropy, native disulfide bonds stabilize the conformation of protein molecules (Dill, 1990), while removal of native disulfides usually causes reduced stability of the target protein (Liu and Cowburn, 2016).
