ATP-binding cassette exporters transport many substrates out of cellular membranes via alternating between inward-facing and outward-facing conformations. Despite extensive research efforts over the past decades, unde...ATP-binding cassette exporters transport many substrates out of cellular membranes via alternating between inward-facing and outward-facing conformations. Despite extensive research efforts over the past decades, understanding of the molecular mechanism remains elusive. As these large-scale conformational movements are global and collective, we have previously performed extensive coarse-grained molecular dynamics simulations of the potential of mean force along the conformational transition pathway [J. Phys. Chem. B 119, 1295(2015)]. However, the occluded conformational state, in which both the internal and external gate are closed, was not determined in the calculated free energy profile. In this work, we extend the above methods to the calculation of the free energy profile along the reaction coordinate, d1-d2, which are the COM distances between the two sides of the internal(d1)and the external gate(d2). The potential of mean force is thus obtained to identify the transition pathway, along which several outward-facing, inward-facing, and occluded state structures are predicted in good agreement with structural experiments. Our coarse-grained molecular dynamics free-energy simulations demonstrate that the internal gate is closed before the external gate is open during the inward-facing to outward-facing transition and vice versa during the inward-facing to outward-facing transition. Our results capture the unidirectional feature of substrate translocation via the exporter, which is functionally important in biology. This finding is different from the previous result, in which both the internal and external gates are open reported in an X-ray experiment [Proc. Natl. Acad. Sci. USA 104,19005(2007)]. Our study sheds light on the molecular mechanism of the state transitions in an ATP-binding cassette exporter.展开更多
The authors offered the new formula of the thermodynamic functions in a magnetic field. The authors have also found that thermodynamic functions of internal energy dUand free energy dF changes in the magnetic field.
Void swelling is an important phenomenon observed in both nuclear fuels and cladding materials in operating nuclear reactors. In this work we develop a phase-field model to simulate void evolution and void volume chan...Void swelling is an important phenomenon observed in both nuclear fuels and cladding materials in operating nuclear reactors. In this work we develop a phase-field model to simulate void evolution and void volume change in irradiated materials. Important material processes, including the generation of defects such as vacancies and self-interstitials, their diffusion and annihilation, and void nucleation and evolution, have been taken into account in this model. The thermodynamic and kinetic properties, such as chemical free energy, interfacial energy, vacancy mobility, and annihilation rate of vacancies and interstitials, are expressed as a function of temperature and/or defect concentrations in a general manner. The model allows for parametric studies of critical void nucleus size, void growth kinetics, and void volume fraction evolutions. Our simulations demonstrated that void swelling displays a quasi-bell shape distribution with temperature often observed in experiments.展开更多
基金supported by the National Natu-ral Science Foundation of China(No.21073170 and No.21273209).
文摘ATP-binding cassette exporters transport many substrates out of cellular membranes via alternating between inward-facing and outward-facing conformations. Despite extensive research efforts over the past decades, understanding of the molecular mechanism remains elusive. As these large-scale conformational movements are global and collective, we have previously performed extensive coarse-grained molecular dynamics simulations of the potential of mean force along the conformational transition pathway [J. Phys. Chem. B 119, 1295(2015)]. However, the occluded conformational state, in which both the internal and external gate are closed, was not determined in the calculated free energy profile. In this work, we extend the above methods to the calculation of the free energy profile along the reaction coordinate, d1-d2, which are the COM distances between the two sides of the internal(d1)and the external gate(d2). The potential of mean force is thus obtained to identify the transition pathway, along which several outward-facing, inward-facing, and occluded state structures are predicted in good agreement with structural experiments. Our coarse-grained molecular dynamics free-energy simulations demonstrate that the internal gate is closed before the external gate is open during the inward-facing to outward-facing transition and vice versa during the inward-facing to outward-facing transition. Our results capture the unidirectional feature of substrate translocation via the exporter, which is functionally important in biology. This finding is different from the previous result, in which both the internal and external gates are open reported in an X-ray experiment [Proc. Natl. Acad. Sci. USA 104,19005(2007)]. Our study sheds light on the molecular mechanism of the state transitions in an ATP-binding cassette exporter.
文摘The authors offered the new formula of the thermodynamic functions in a magnetic field. The authors have also found that thermodynamic functions of internal energy dUand free energy dF changes in the magnetic field.
基金supported by the US Department of Energy’s Nuclear Energy Advance Modeling and Simulation (NEAMS) Program in Pacific Northwest National Laboratory, which is operated by Battelle Memorial Institute for the US Department of Energy (Grant No. DE-AC05- 76RL01830)Two of the authors (LI YuLan and GAO Fei) were partially supported by the Materials Sciences and Engineering Division, Office of Basic Energy Sciences, US Department of Energy
文摘Void swelling is an important phenomenon observed in both nuclear fuels and cladding materials in operating nuclear reactors. In this work we develop a phase-field model to simulate void evolution and void volume change in irradiated materials. Important material processes, including the generation of defects such as vacancies and self-interstitials, their diffusion and annihilation, and void nucleation and evolution, have been taken into account in this model. The thermodynamic and kinetic properties, such as chemical free energy, interfacial energy, vacancy mobility, and annihilation rate of vacancies and interstitials, are expressed as a function of temperature and/or defect concentrations in a general manner. The model allows for parametric studies of critical void nucleus size, void growth kinetics, and void volume fraction evolutions. Our simulations demonstrated that void swelling displays a quasi-bell shape distribution with temperature often observed in experiments.
