Docking and molecular dynamics studies toward the binding of new natural phenolic marine inhibitors and aldose reductase

Phenolic marine natural product is a kind of new potential aldose reductase inhibitors (ARIs). In order to investigate the binding mode and inhibition mechanism, molecular docking and dynamics studies were performed to explore the interactions of six phenolic inhibitors with human aldose reductase (hALR2). Considering physiological environment, all the neutral and other two ionized states of each phenolic inhibitor were adopted in the simulation. The calculations indicate that all the inhibitors are able to form stable hydrogen bonds with the hALR2 active pocket which is mainly constructed by residues TYR48, HIS110 and TRP111, and they impose the inhibition effect by occupying the active space. In all inhibitors, only La and its two ionized derivatives La_ion1 and La_ion2, in which neither of the ortho-hydrogens of 3-hydroxyl is substituted by Br, bind with hALR2 active residues using the terminal 3-hydroxyl. While, all the other inhibitors, at least one of whose ortho-sites of 3- and 6-hydroxyls are substituted by Br substituent which take much electron-withdrawing effect and steric hindrance, bind with hALR2 through the lactone group. This means that the Br substituent can effectively regulate the binding modes of phenolic inhibitors. Although the lactone bound inhibitors have relatively high RMSD values, our dynamics study shows that both binding modes are of high stability. For each inhibitor molecule, the ionization does not change its original binding mode, but it does gradually increase the binding free energy, which reveals that besides hydrogen bonds, the electrostatic effect is also important to the inhibitor–hALR2 interaction.

北京石花洞滴水沉积的季节变化及影响因素

Because of the high resolution, stalagmite laminae can play an important role in the paleoclimate reconstructions. However, few investigations for the formation mechanisms of stalagmite lamilae have been done. Based on two-year observation on calcite growth rate at the drip sites, three-year monitoring of hydrodynamics, physics and chemistry of drip waters at different drip sites and the surrounding environments inside and outside the Beijing Shihua Cave, the seasonal variations of calcite growth rate are revealed and the results can be concluded as follows: 1. The drip waters inside the Cave are mostly sourced from the summer rain, and its minimal response-time to the atmospheric precipitation is less than one day. There are three types of response relationships between the precipitation and the drip rate variations: rapid response type, time-lag response type and stable response type. For rapid response type, the drip discharge is recharged through the flow routes along intensive fractures and interconnectivities; for time-lag response type, the drip discharge is recharged by double-porosity system composed of a high conductivity, low storage capability conduit network and a low-conductivity high-storage capability rock matrix under variable boundary conditions; for stable response type, the drip discharge is mainly recharged by seepage flow and base flow. 2. The observation shows that, inside the Cave, the growth rate of calcite is generally lower in rainy seasons and higher in dry seasons. During the rainy seasons, the drip water is characterized by a lower pH value, higher [Ca2+], [Mg2+], [SO42-] and electrical conductivity (EC) values. According to the calculations of saturation index of calcite (SIc), pCO2 of the drip water, as well as the synthetical analysis of other possible factors, the calcite growth rate is found to be principally influenced by the drip water saturation index of calcite (SIc). And the drip rate and pCO2 in the drip water and in the cave air play the secondly important roles in this process. The recharge mode of heavy rainfall events in the rainy seasons should probably be the main driving force that controls the physicochemical properties and calcite sediment of the drip waters. The abrupt decrease of sedimentary rate and the sharp peak of DOC in drip water in the rainy season probably forms the thin opaque (luminescent under ultraviolet radiation) layers observed in the stalagmites, whereas the relatively higher sedimentary rate in the dry seasons may be responsible for the thicker bright layers. The investigation elucidated here preliminarily reveals the formation mechanism of the stalagmite laminae in Beijing Shihua Cave.

南海北部大陆边缘盆地深部地热特征用地球动力学演化

This report is a conclusion of the major research outcome during my post-doctoral residence of research and work. Its content covers the researches of the deep thermal characteristic and dynamics evolution beneath the northern margin basin of South China Sea. In this report, the each other action and effect between lithosphere ad mantle convection were regarded by the combine of deep and shallow study, subdivision from whole to part, and pay equal attention to determine the nature and fixed quantity. The investigative method we used in this report is geothermal and gravity methods. By the help of geological model and geophysics modeling, we calculated lithosphere thermal structure, rheology structure and mantle convection. Firstly, the report introduces concisely the purpose and the previous achievement to this research. Then, it analyzed the characteristic of heat flow on South China Sea. The structure of deep temperature and thermal has been calculated in some models of heat generation and conduction. The rock rheology structure also was computed by the relationship between temperature and viscosity. All these calculations were finished under the guidelines of combine with geology and geophysics. Meanwhile, the fields both deep mantle convection and small scale upper mantle convection are computed. Beside, the density and temperature disorder resulted by mantle convection were also computed with the convection field. After these, the report bring the contribution of local field of mantle convection, thermal construct and effective viscosity beneath the northern margin basin of South China Sea. And, base on the tectonic background and evolution feature, this report discussion the evolution mechanism of south China Sea and its northern margin basin. The end of this report, the main conclusion of this research was summarized and brings out.