Effects of Transcutaneous Electrical Acupoint Stimulation on the Plasma Amino Acid and Extracellular 5-HT in Dorsal Raphe Nucleus of Exercising Rats / 中国运动医学杂志

Objective To observe the effect of transcutanous electrical acupoint stimulation(TEAS)on the exercise ability of rats.Methods After stereotaxis surgery,twenty male adult SD rats wera randomly divided into control group (n=10)and TEAS group(n=10).Two days after surgery.the rats were trained to adapt the treadmill mnning and TEAS(continuous wave,2Hz,5mA)was applied to right Zusanli (ST 36) for 30min,once a day for 6 days.Basic microdialysis samples of extracellular serotonin(5-HT)in rats'dorsal raphe nucleus(DRN)were collected 7 days after surgery.During experiment,rats were running on treadmill (10m/min for 10min,then gradually increased to 24m/min for 1 hour,0% grade).Microdialysis samples were collected continuously until 5 hours after treadmill running.The frequency of brush-stimulation during the running was recorded.Meanwhile,plasma amino acid content was examined 5 hours after exercise.Results The frequencies of brush-stimulation during the treadmill running in control group and TEAS group were 2.04+0.46 and 0.40+0.080 times per minute,respectively (P0.05).However,plasma free-TRP(f-TRP)content,f-TRP/T-TRP ratio and f-TRP/BCAA ratio decreased significantly(P<0.05) in TEAS group as compared with the control group.Extracellular 5-HT levels in DRN in control group soon after exercise were higher than their base levels(P<0.05),and decreased in sequential two hours,and then increased significantly 3 hours and 4 hours after exercise as compared with that 2 hours after exercise(P<0.05).There was a slow decline in the levels of extracellular 5-HT in TEAS group at each time-point after exercise,and significant lower than that in control group within 5 hours after exercise(P<0.05).Conclusion TEAS atZusanli(ST36)can effectively improve exercised ability by reducing peripheral free-TRP level and transporting TRP into the brain,and thus decreasing the synthesis of 5-HT in the brain.

A Study on Drug Resistance Mechanism of HIV-1 Integrase Mutants by Molecular Modeling / 生物化学与生物物理进展

The drug resistant mutations in human immunodefieiency virus type 1 (HIV-1) are a major impediment to successful highly active antiretrovirai therapy (HAART) and new drug design. In order to understand the drug resistance mechanism of HIV-1 integrase (IN) mutually existed for multiple drug-resistant strains to the most potent IN inhibitors diketo acids (DKAs), three S-1360-resistant HIV-1 strains were selected and molecular docking and molecular dynamics (MD) simulations were performed to obtain the inhibitor binding modes. Based on the binding modes, compelling differences between the wild-type and the 3 mutants for IN have been observed. The results showed that: 1) In the mutants, the inhibitor is close to the funetional loop 3 region but far away from the DNA binding site. Different binding sites lead to the decrease in susceptibility to S-1360 in mutants compared to the wild-type IN. 2) The fluctuations in the region of residues 138～166 are important to the biological function of IN. 2 hydrogen-bonds between S-1360 with residues N155 and K159 restrict the flexibility of the region. Drug resistant mutations result in a lack of the interaction, consequently, the less susceptible to S-1360. 3) In the 3 mutant IN complexes, the benzyl ring of S-1360 is far from the viral DNA binding site, thus, S-1360 can not prevent the end of the viral DNA from exposure to human DNA. 4) After T66I mutation, the long side chain of I occupied the active pocket in the 3 mutants, consequently, the inhibitor could not move into the same binding site or have the same orientation. All the above contribute to drug resistance. These results will be useful for the rational inhibitor modify and design.

Progress in Protein-protein Docking Approaches / 生物化学与生物物理进展

Protein-protein interactions and recognition are the focal and hot themes of the life science field in the 21st century. Molecular docking approach is the effective computer modeling technology in the study of this topic. Generally, the protein-protein docking procedure is composed of four stages: searching of the binding modes of the receptor and the ligand, filtering of docked modes to eliminate the irrational docked structures, optimizing the structures, evaluating the docked modes with the refined scoring function and ranking them to obtain the near-native structures. Combining the research group's works, in terms of the international and national progress of protein-protein docking approaches, the detailed review was made about the four stages mentioned above. Additionally, the existing major questions are analyzed and the prospects of the future study are made.

Protein Folding Study Based on The HNP Model and The Relative Entropy Approach / 生物化学与生物物理进展

Twenty kinds of amino acids are simplified into 3 types: hydrophobic amino acids (H), hydrophilic amino acids (P) and neutral amino acids (N). Each residue is reduced to a bead which locates in the position of the C?琢 atom. The off-lattice model is adopted and the relative entropy is used as a minimization function to predict the tertiary structure of a protein. A new contact intensity function is given to consist with protein design research based on the relative entropy. Testing on several real proteins from Protein Data Bank (PDB) shows the good results obtained with the model and method. The root mean square deviations (RMSD) of the predicted structures relative to the native structures range from 0.30 to 0.70 nm. A foundation for studying protein design using the HNP model and the relative entropy was made.

Application of Protein Design Method Based on The HNP Model and Relative Entropy for Different Protein Systems / 生物化学与生物物理进展

The application of the protein design method based on the HNP model and the relative entropy theory is discussed for four structural classes of real proteins, and the results are compared with that of the HP model. Testing on 190 proteins shows that this method is generally effective for the different structural classes of proteins. Further studies show that the success rate of this method on regular secondary structures is higher than that on the random coil. Additionally, the success rate for different types of amino acids is also analyzed. It is found that the success rate on the hydrophilic residues is higher than those of the other two types. Furthermore, the success rate of this method on the conserved residues is higher than the non-conserved residues. The reasons resulting in the difference of the success rate on different systems were also analyzed. All analyses mentioned above make the foundation for the development and the application of this method in the future.