Structural and functional characterization of the human CCR5 receptor in complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular modeling studies

The entry of human immunodeficiency virus (HIV) into cells depends on a sequential interaction of the gp120 envelope glycoprotein with the cellular receptors CD4 and members of the chemokine receptor family. The CC chemokine receptor CCR5 is such a receptor for several chemokines and a major coreceptor for the entry of R5 HIV type-1 (HIV-1) into cells. Although many studies focus on the interaction of CCR5 with HIV-1, the corresponding interaction sites in CCR5 and gp120 have not been matched. Here we used an approach combining protein structure modeling, docking and molecular dynamics simulation to build a series of structural models of the CCR5 in complexes with gp120 and CD4. Interactions such as hydrogen bonds, salt bridges and van der Waals contacts between CCR5 and gp120 were investigated. Three snapshots of CCR5-gp120-CD4 models revealed that the initial interactions of CCR5 with gp120 are involved in the negatively charged N-terminus (Nt) region of CCR5 and positively charged bridging sheet region of gp120. Further interactions occurred between extracellular loop2 (ECL2) of CCR5 and the base of V3 loop regions of gp120. These interactions may induce the conformational changes in gp120 and lead to the final entry of HIV into the cell. These results not only strongly support the two-step gp120-CCR5 binding mechanism, but also rationalize extensive biological data about the role of CCR5 in HIV-1 gp120 binding and entry, and may guide efforts to design novel inhibitors.

Adlayer Structures of DL-Homocysteine and L-Homocysteine Thiolactone on Au(111) Surface: an in situ STM Study

The adsorption Of DL-homocysteine (Hcy) and L-homocysteine thiolactone (HTL) on Au(1 1 1) electrode was investigated in 0.1 M HClO4 by cyclic voltammetry and in situ scanning tunneling microscopy (STM). Hcy and HTL molecules formed highly ordered adlayers on Au(1 1 1) surface. High-resolution STM images revealed the orientation and packing arrangement in the ordered adlayers. Hcy molecules formed (2root3 x 3root3)R30degrees adlayer structure and H-bonds between carboxyl groups were assumed to be responsible for the origin of tail-to-tail or head-to-head molecular arrangement, while HTL molecules formed (4 x 6) adlayer structure, and two different orientations and appearances in the ordered adlayer were found. Structural models were proposed for the two adlayers.

Recent advance in the study of ribosomal model.

With the technological developments of cryoelectron microscope, X-ray diffraction and the growing data available on various components of ribosome, some marvelously intricate structural models of the Escherichia coli 70S ribosome have been reconstructed. The picture of the ribosomal model are detailed, including the placement of the mRNA, the arrangement of the A-site and P-site tRNAs and the peptidyltransferase within the interface gap as well as the path of nascent polypeptide chain, which results in a better understanding of the structure and function of ribosome as well as the translational process.

焦虑的因素结构及其在中学生中的验证

Since anxiety exists as a certain kind of relation between the subject and his stimuli, present study proposed the criterion that every one of the anxiety’s structural components had to manifest the properties of the relation, not the subject’s properties, and not the stimuli’s properties, too; and that every component must be a bridge from the subject to the object. Several structural models on anxiety were judged by the criterion, and three suited factors were drawn out, which were controllability, importance and urgency. Then through various methods of interview, questionnaire, laboratorial experiment, events graded, the research examined the relations between the three factors and normal anxiety, and explored the interaction of controllability, importance and urgency when they worked together. The results were as the following: 1. The hypothesis that controllability, importance and urgency were the structural components of normal anxiety sounds reasonable, which was supported in different degrees by the results of several secondary research with various methods. 2. With a totally different method of constructing items from the prevalent integrative anxiety inventory, an effective normal anxiety inventory of middle school students was developed based on this theoretical consideration. Reliability and validity research showed that the coefficient of homogeneity and test-retest reliability were high. The construct validity and criterion validity were good enough. The inventory was a useful scale to measure the normal anxiety for middle school students. 3. It’s through their interaction that controllability and importance effect on the level of anxiety which was produced by the relevant event. 4. Anxiety arises with the increasing of importance or urgency. Though there’s a very close connection between controllability and anxiety, the concrete situation is very complicated. Not only is the level of anxiety affected by the interaction of controllability and importance, but when controllability tends to be extremely high or extremely low, importance may also begin to vary with controllability. What’s more, dispositional optimism and self-efficacy still exert influences that cannot be ignored on the relationship between controllability and anxiety. All the results indicated that it was reasonable to regard and study anxiety as a kind of relation between the subject and his environment, and to some extent it’s even necessary if the intention was to clarify the structure of anxiety. Since all the other emotion also exists as a kind of relation between the subject and his stimuli, the wholeness principle which was first proposed and recommended in this study will be of great value to the related researchers. And the interaction between controllability and importance may suggest a valid coping strategy of anxiety.

Structural analysis of human CCR2b and primate CCR2b by molecular modeling and molecular dynamics simulation

CCR2b, a chemokine receptor for MCP-1, -2, -3, -4, plays an important role in a variety of diseases involving infection, inflammation, and/or injury, as well as being a coreceptor for HIV-1 infection. Two models of human CCR2b (hCCR2b) were generated by h

Structural selectivity of aromatic diamidines

Competition dialysis was used to study the interactions of 13 substituted aromatic diamidine compounds with 13 nucleic acid structures and sequences. The results show a striking selectivity of these compounds for the triplex structure poly dA:(poly dT)(2), a novel aspect of their interaction with nucleic acids not previously described. The triplex selectivity of selected compounds was confirmed by thermal denaturation studies. Triplex selectivity was found to be modulated by the location of amidine substiuents on the core phenyl-furan-phenyl ring scaffold. Molecular models were constructed to rationalize the triplex selectivity of DB359, the most selective compound in the series. Its triplex selectivity was found to arise from optimal ring stacking on base triplets, along with proper positioning of its amidine substituents to occupy the minor and the major-minor grooves of the triplex. New insights into the molecular recognition of nucleic acid structures emerged from these studies, adding to the list of available design principles for selectively targeting DNA and RNA.