Study on the interaction of paeoniflorin with human serum albumin (HSA) by spectroscopic and molecular docking techniques.

The interaction of paeoniflorin with human serum albumin (HSA) was investigated using fluorescence, UV-vis absorption, circular dichroism (CD) spectra and molecular docking techniques under simulative physiological conditions. The results clarified that the fluorescence quenching of HSA by paeoniflorin was a static quenching process and energy transfer as a result of a newly formed complex (1:1). Paeoniflorin spontaneously bound to HSA in site I (subdomain IIA), which was primarily driven by hydrophobic forces and hydrogen bonds (ΔH° = - 9.98 kJ mol-1, ΔS° = 28.18 J mol-1 K-1). The binding constant was calculated to be 1.909 × 103 L mol-1 at 288 K and it decreased with the increase of the temperature. The binding distance was estimated to be 1.74 nm at 288 K, showing the occurrence of fluorescence energy transfer. The results of CD and three-dimensional fluorescence spectra showed that paeoniflorin induced the conformational changes of HSA. Meanwhile, the study of molecular docking also indicated that paeoniflorin could bind to the site I of HSA mainly by hydrophobic and hydrogen bond interactions.

Virtual screening approach to identifying influenza virus neuraminidase inhibitors using molecular docking combined with machine-learning-based scoring function.

In recent years, an epidemic of the highly pathogenic avian influenza H7N9 virus has persisted in China, with a high mortality rate. To develop novel anti-influenza therapies, we have constructed a machine-learning-based scoring function (RF-NA-Score) for the effective virtual screening of lead compounds targeting the viral neuraminidase (NA) protein. RF-NA-Score is more accurate than RF-Score, with a root-mean-square error of 1.46, Pearson's correlation coefficient of 0.707, and Spearman's rank correlation coefficient of 0.707 in a 5-fold cross-validation study. The performance of RF-NA-Score in a docking-based virtual screening of NA inhibitors was evaluated with a dataset containing 281 NA inhibitors and 322 noninhibitors. Compared with other docking-rescoring virtual screening strategies, rescoring with RF-NA-Score significantly improved the efficiency of virtual screening, and a strategy that averaged the scores given by RF-NA-Score, based on the binding conformations predicted with AutoDock, AutoDock Vina, and LeDock, was shown to be the best strategy. This strategy was then applied to the virtual screening of NA inhibitors in the SPECS database. The 100 selected compounds were tested in an in vitro H7N9 NA inhibition assay, and two compounds with novel scaffolds showed moderate inhibitory activities. These results indicate that RF-NA-Score improves the efficiency of virtual screening for NA inhibitors, and can be used successfully to identify new NA inhibitor scaffolds. Scoring functions specific for other drug targets could also be established with the same method.

Probing the binding reaction of cytarabine to human serum albumin using multispectroscopic techniques with the aid of molecular docking.

Cytarabine is a kind of chemotherapy medication. In the present study, the molecular interaction between cytarabine and human serum albumin (HSA) was investigated via fluorescence, UV-vis absorption, circular dichroism (CD) spectroscopy and molecular docking method under simulative physiological conditions. It was found that cytarabine could effectively quench the intrinsic fluorescence of HSA through a static quenching process. The apparent binding constants between drug and HSA at 288, 293 and 298K were estimated to be in the order of 103L·mol-1. The thermodynamic parameters ΔH°, ΔG°and ΔS° were calculated, in which the negative ΔG°suggested that the binding of cytarabine to HSA was spontaneous, moreover the negative ΔS°and negative ΔH°revealed that van der Waals force and hydrogen bonds were the major forces to stabilize the protein-cytarabine (1:1) complex. The competitive binding experiments showed that the primary binding site of cytarabine was located in the site I (subdomain IIA) of HSA. In addition, the binding distance was calculated to be 3.4nm according to the Förster no-radiation energy transfer theory. The analysis of CD and three-dimensional (3D) fluorescence spectra demonstrated that the binding of drug to HSA induced some conformational changes in HSA. The molecular docking study also led to the same conclusion obtained from the spectral results.

Paenibacillusliaoningensis sp. nov., isolated from soil.

A novel bacterial strain, designated as LNUB461T, was isolated from soil sample taken from the countryside of Shenyang, Liaoning Province, China. The isolate was a Gram-stain-positive, aerobiotic, motile, endospore-forming and rod-shaped bacterium. The organism grew optimally at 30-33 °C, pH 6.5-7.0 and in the absence of NaCl. Phylogenetic analysis based on the nearly full-length 16S rRNA gene sequence revealed high sequence similarity with Paenibacillus algorifonticola XJ259T (98.5 %), Paenibacillus xinjiangensis B538T (96.8 %), Paenibacillus glycanilyticus DS-1T (96.1 %) and Paenibacillus lupini RLAHU15T (96.1 %). The predominant cellular fatty acid and the only menaquinone were anteiso-C15:0 and MK-7, respectively. The main polar lipids of LNUB461T included phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC) and two unknown amino phospholipids (APL), and the cell-wall peptidoglycan was meso-diaminopimelic acid (A1γ). The DNA G+C content of LNUB461T was 49.1 mol%. The DNA-DNA hybridization value between LNUB461T and the most closely related species (P. algorifonticola) was 41.8 %. On the basis of these data, LNUB461T was classified as representing a novel species of the genus Paenibacillus, for which the name Paenibacillus liaoningensis sp. nov was proposed. The type strain is LNUB461T (=JCM 30712T=CGMCC 1.15101T).