Study of Endogen Substrates,Drug Substrates and Inhibitors Binding Conformations on MRP4 and Its Variants by Molecular Docking and Molecular Dynamics

Multidrug resistance protein-4 (MRP4) belongs to the ABC transporter superfamily and promotes the transport of xenobiotics including drugs. A non-synonymous single nucleotide polymorphisms (nsSNPs) in the ABCC4 gene can promote changes in the structure and function of MRP4. In this work, the interaction of certain endogen substrates, drug substrates, and inhibitors with wild type-MRP4 (WT-MRP4) and its variants G187W and Y556C were studied to determine differences in the intermolecular interactions and affinity related to SNPs using protein threading modeling, molecular docking, all-atom, coarse grained, and umbrella sampling molecular dynamics simulations (AA-MDS and CG-MDS, respectively). The results showed that the three MRP4 structures had significantly different conformations at given sites, leading to differences in the docking scores (DS) and binding sites of three different groups of molecules. Folic acid (FA) had the highest variation in DS on G187W concerning WT-MRP4. WT-MRP4, G187W, Y556C, and FA had different conformations through 25 ns AA-MD. Umbrella sampling simulations indicated that the Y556C-FA complex was the most stable one with or without ATP. In Y556C, the cyclic adenosine monophosphate (cAMP) and ceefourin-1 binding sites are located out of the entrance of the inner cavity, which suggests that both cAMP and ceefourin-1 may not be transported. The binding site for cAMP and ceefourin-1 is quite similar and the affinity (binding energy) of ceefourin-1 to WT-MRP4, G187W, and Y556C is greater than the affinity of cAMP, which may suggest that ceefourin-1 works as a competitive inhibitor. In conclusion, the nsSNPs G187W and Y556C lead to changes in protein conformation, which modifies the ligand binding site, DS, and binding energy.     

LaMnO3不同晶位掺杂的磁电阻效应

基于研究钙钛矿型氧化物磁电阻效应的目的,采用固相反应法制备了实验所需的单相多晶样品,主要就La位二价金属离子掺杂和稀土互掺及Mn位掺杂对LaMnO3磁电阻影响的实验结果作比较研究,发现La位稀土互掺对磁电阻的影响可以用晶格效应来解释,并明确指出La位和Mn位掺杂是提高和调制钙钛矿型锰氧化物超大磁电阻效应的一种有效途径.     

多元有序地质数据的最优分割法在工程中的应用

采用数学地质理论中的多元有序地质数据的最优分割方法对工程场地松散岩土层亚层进行了划分。实践证明 ,在土样物理力学性能评价指标选取合理的前提下 ,该方法简单方便 ,行之有效 ,可作为一种辅助手段帮助地质人员开展对土层的详细研究     

Quadrupole interactions at 57Fe and 119Sn in 3d-metal antimonides

3d-metal antimonides: Fe_1+x Sb, N_+x Sb, Co_+x Sb and the (Ni_1?y Fe _y )Sb solid solution have been studied by the Mössbauer effect method at ⁵⁷Fe and ¹¹⁹Sn. It was found that the quadrupole interactions at the Fe and Sn nucleus in 3d-metal antimonides are very sensitive to the filling of different crystallographic sites with metal atoms. The metal atoms in trigonal-bipyramidal sites have a strong effect on the quadrupole splitting of ¹¹⁹Sn. They are nearest to anions (Sb or Sn) with the typical axial ratio of c/a = 1.25. The QS(x) dependence of ¹¹⁹ Sn in 3d-metal antimonides in the 0 ≤ x ≤ 0.1 concentration range can be used to determine x – the concentration of transition metal excess relative to the stoichiometric composition.     

Fluorescence line narrowed spectra of Zn and metal-free cytochrome c

Fluorescence line narrowing (FLN) spectroscopy was used to study the role of the polypeptide chain in influencing the spectrum of Zn-substituted cytochrome c (Zn cyt c) and metal-free cyt c (porphyrin cyt c). For both derivatives the spectra show characteristics of relaxed fluorescence from an inhomogeneously broadened sample. Zero phonon lines and phonon wings can be clearly distinguished, and vibrational frequencies of the ground and excited states were identified. The inhomogeneous distribution width for porphyrin cyt c is slightly wider than that of Zn cyt c and a second population of molecules was apparent in the porphyrin cyt c. The phonon coupling was greater for Zn cyt c than for porphyrin cyt c, which may be due to the extra coupling to the polypeptide chain by metal ligation.This work has been done in partial fulfillment of the requirements for the Doctor of Philosophy degree.     

拥挤型网络的路流组合及模型求解的搜索法

证明了一个路流组合定理并由此而给出了一个求解网络选址两级模型的算法，讨论了网络的Ｂｒａｅｓｓ性及其在网络规划中的应用前景。     

长江中游平原地区黑杨派南方型无性系立地质量评价——Ⅰ.土壤-立地因子分析

影响黑杨派南方型无性系生长的综合土壤-立地因子有:有效水分、物理性状、通气条件和土壤养分.综合土壤-立地因子由反映立地质量的土壤-立地子因子构成.通径分析表明:影响土壤有效水分的土壤-立地子因子主要是局域位置、地形条件和地下水位;影响物理性状的是质地与结构;影响通气条件的是经营水平;而影响土壤养分的土壤-立地子因子是速效钾和pH值.     

平原农田防护林杨树生长模型及应用研究

应用MATLAB6．5软件，采用经典理论生长方程Logistic方程、Richards方程、单分子式（Mitscherlich）方程对苏北平原建湖县农田防护林I-72杨的平均高、优势高、平均胸径、平均材积生长数据进行曲线拟合．结果表明，Logistic方程拟合胸径、平均高生长效果最好，而Richards方程拟合优势高、材积生长效果最好，并运用拟合模型结果进行立地质量评价和成熟龄确定．     

Quantum chemistry investigation on the active site of Mn-SOD

In this paper, we carried out a theoretical study on the active site structures of the Mn-SOD with ab initio Hartree–Fock SCF method, and analyzed the molecular orbital energies, charges and atomic orbital contribution to the frontier molecular orbital.