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
Thermally driven diffusive motion of a particle underlies many physical and biological processes. In the presence of traps and obstacles, the spread of the particle is substantially impeded, leading to subdiffusive sc...Thermally driven diffusive motion of a particle underlies many physical and biological processes. In the presence of traps and obstacles, the spread of the particle is substantially impeded, leading to subdiffusive scaling at long times. The statistical mechanical treatment of diffusion in a disordered environment is often quite involved. In this short review, we present a simple and unified view of the many quantitative results on anomalous diffusion in the literature, including the scaling of the diffusion front and the mean first-passage time. Varioust analytic calculations and physical arguments are examined to highlight the role of dimensionality, energy landscape, and rare events in affecting the particle trajectory statistics. The general understanding that emerges will aid the interpretation of relevant experimental and simulation results.展开更多
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. 11175013)the Research Grants Council of the Hong Kong Special Administrative Region,China (Grant No. N HKBU 213/10)
文摘Thermally driven diffusive motion of a particle underlies many physical and biological processes. In the presence of traps and obstacles, the spread of the particle is substantially impeded, leading to subdiffusive scaling at long times. The statistical mechanical treatment of diffusion in a disordered environment is often quite involved. In this short review, we present a simple and unified view of the many quantitative results on anomalous diffusion in the literature, including the scaling of the diffusion front and the mean first-passage time. Varioust analytic calculations and physical arguments are examined to highlight the role of dimensionality, energy landscape, and rare events in affecting the particle trajectory statistics. The general understanding that emerges will aid the interpretation of relevant experimental and simulation results.
