Prediction of Inter-residue Multiple Distances and Exploration of Protein Multiple Conformations by Deep Learning.

AlphaFold2 has achieved a major breakthrough in end-to-end prediction for static protein structures. However, protein conformational change is considered to be a key factor in protein biological function. Inter-residue multiple distances prediction is of great significance for research on protein multiple conformations exploration. In this study, we proposed an inter-residue multiple distances prediction method, DeepMDisPre, based on an improved network which integrates triangle update, axial attention and ResNet to predict multiple distances of residue pairs. We built a dataset which contains proteins with a single structure and proteins with multiple conformations to train the network. We tested DeepMDisPre on 114 proteins with multiple conformations. The results show that the inter-residue distance distribution predicted by DeepMDisPre tends to have multiple peaks for flexible residue pairs than for rigid residue pairs. On two cases of proteins with multiple conformations, we modeled the multiple conformations relatively accurately by using the predicted inter-residue multiple distances. In addition, we also tested the performance of DeepMDisPre on 279 proteins with a single structure. Experimental results demonstrate that the average contact accuracy of DeepMDisPre is higher than that of the comparative method. In terms of static protein modeling, the average TM-score of the 3D models built by DeepMDisPre is also improved compared with the comparative method. The executable program is freely available at https://github.com/iobio-zjut/DeepMDisPre.

Protein structure and folding pathway prediction based on remote homologs recognition using PAthreader.

Recognition of remote homologous structures is a necessary module in AlphaFold2 and is also essential for the exploration of protein folding pathways. Here, we propose a method, PAthreader, to recognize remote templates and explore folding pathways. Firstly, we design a three-track alignment between predicted distance profiles and structure profiles extracted from PDB and AlphaFold DB, to improve the recognition accuracy of remote templates. Secondly, we improve the performance of AlphaFold2 using the templates identified by PAthreader. Thirdly, we explore protein folding pathways based on our conjecture that dynamic folding information of protein is implicitly contained in its remote homologs. The results show that the average accuracy of PAthreader templates is 11.6% higher than that of HHsearch. In terms of structure modelling, PAthreader outperform AlphaFold2 and ranks first on the CAMEO blind test for the latest three months. Furthermore, we predict protein folding pathways for 37 proteins, in which the results of 7 proteins are almost consistent with those of biological experiments, and the other 30 human proteins have yet to be verified by biological experiments, revealing that folding information can be exploited from remote homologous structures.

Symmetry-Broken Intermolecular Charge Separation of Cationic Radicals.

A quadrupolar compound Pyr-BA with two pyrrole-type nitrogen atoms doped externally was prepared in this work. In high contrast with other π ionic radicals, its cationic radical Pyr-BA⋅+ undergoes unusual symmetry-broken charge separation (SB-CS), generating the mixed valence complex of Pyr-BA+1-q ⋅⋅⋅Pyr-BA+1+q , where q is the degree of charge transfer. Variable-temperature (VT) single-crystal analysis, absorption and EPR experiments all confirmed that aggregation and lower temperature would help to facilitate this SB-CS process. Gibbs energy calculations and gauge-including magnetically induced current simulation both validate that, for Pyr-BA⋅+ , SB-CS behavior is more favorable than the conventional dimerization mode. To the best of our knowledge, this is the first study that shows solid single-crystal evidence for spontaneous SB-CS between identical ionic radicals. Such a unique phenomenon is of great significance both in terms of fundamental aspects and uncharted material science.

Distribution, sources, and ecological risk assessment of polycyclic aromatic hydrocarbons in the sediments of Daihai Lake in Inner Mongolia, China.

Polycyclic aromatic hydrocarbons (PAHs) are typical toxic organic pollutants that can accumulate in sediments and may be toxic to aquatic organisms. In the present study, the contamination level, composition pattern, and sources of sixteen PAHs listed by the United States Environmental Protection Agency were investigated in surface sediments and a sediment core from Daihai Lake, which is located in a typical semiarid area of Inner Mongolia, China, and the ecological risk of these PAHs was assessed. The results show that the total concentration of PAHs in the surface sediments ranged from 204.6 to 344.5 ng/g with an average value of 287.2 ng/g and that compared with other aquatic systems, the level of PAHs in the sediments from Daihai Lake was low. However, a general upward trend was observed for the concentrations of PAHs in the sediment core, which might be related to the increase in human activities in the area. Moreover, the PAH concentrations were significantly positively correlated with the total organic carbon (TOC) content in the sediments, and it is thus inferred that TOC regulates the distribution of PAHs in Daihai Lake. Three-ring and four-ring PAHs were found to be predominant in all the sediment samples, and phenanthrene (Phe) was the most abundant compound. According to the composition of PAHs and the anthracene (Ant)/(Ant+Phe) or fluoranthene (Flt)/(Flt+pyrene (Pyr)) ratios, the PAHs in Daihai Lake mainly originated from the combustion of domestic coal, grass, and wood, and petroleum cannot be ignored as a source considering the growth of industry. Risk assessment based on a comparison of PAH concentrations and the effect range low (ERL) and effect range median (ERM) values demonstrated that acenaphthene (Ace) at 11 sites and fluorene (Flu) at 7 sites had occasional adverse biological effects.

Effects of environmental factors on nutrients release at sediment-water interface and assessment of trophic status for a typical shallow lake, northwest China.

Surface sediment and water samples were collected from Daihai Lake to study the biogeochemical characteristics of nitrogen and phosphorus, to estimate the loads of these nutrients, and to assess their effects on water quality. The contents and spatial distributions of total phosphorus (TP), total nitrogen (TN), and different nitrogen forms in sediments were analyzed. The results showed that concentrations of TN and TP in surface sediments ranged from 0.27 to 1.78 g/kg and from 558.31 to 891.29 mg/kg, respectively. Ratios of C:N ranged between 8.2 and 12.1, which indicated that nitrogen accumulated came mainly from terrestrial source. Ratios of N:P in all sampling sites were below 10, which indicated that N was the limiting nutrient for algal growth in this lake. Effects of environment factors on the release of nitrogen and phosphorus in lake sediments were also determined; high pH values could encourage the release of nitrogen and phosphorus. Modified Carlson's trophic state index (TSI(M)) and comprehensive trophic state index (TSI(C)) were applied to ascertain the trophic classification of the studied lake, and the values of TSI(M) and TSI(C) ranged from 53.72 to 70.61 and from 47.73 to 53.67, respectively, which indicated that the Daihai Lake was in the stage of hypereutropher.

Spatial and seasonal variations of pesticide contamination in agricultural soils and crops sample from an intensive horticulture area of Hohhot, North-West China.

The spatial variability and temporal trend in concentrations of the organochlorine pesticides (OCPs), hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethane (DDT), in soils and agricultural corps were investigated on an intensive horticulture area in Hohhot, North-West China, from 2008 to 2011. The most frequently found and abundant pesticides were the metabolites of DDT (p,p'-DDE, p,p'-DDT, o,p'-DDT and p,p'-DDD). Total DDT concentrations ranged from ND (not detectable) to 507.41 ng/g and were higher than the concentration of total HCHs measured for the range of 4.84-281.44 ng/g. There were significantly positive correlations between the ∑DDT and ∑HCH concentrations (r (2)>0.74) in soils, but no significant correlation was found between the concentrations of OCPs in soils and clay content while a relatively strong correlation was found between total OCP concentrations and total organic carbon (TOC). ß-HCH was the main isomer of HCHs, and was detected in all samples; the maximum proportion of ß-HCH compared to ∑HCHs (mean value 54%) was found, suggesting its persistence. The α/γ-HCH ratio was between 0.89 and 5.39, which signified the combined influence of technical HCHs and lindane. Low p,p'-DDE/p,p'-DDT in N1, N3 and N9 were found, reflecting the fresh input of DDTs, while the relatively high o,p'-DDT/p,p'-DDT ratios indicated the agricultural application of dicofol. Ratios of DDT/(DDE+DDD) in soils do not indicate recent inputs of DDT into Hohhot farmland soil environment. Seasonal variations of OCPs featured higher concentrations in autumn and lower concentrations in spring. This was likely associated with their temperature-driven re-volatilization and application of dicofol in late spring.

Anti-allergic effects of total bakkenolides from Petasites tricholobus in ovalbumin-sensitized rats.

The anti-allergic effect of total bakkenolides from the rhizome of Petasites tricholobus (BAPT) was evaluated in an ovalbumin-induced allergic rhinitis model in male Wistar rats. The major components of the bakkenolide fraction are bakkenolide-D, bakkenolide-B, bakkenolide-IIIa and bakkenolide-IVa, which account for 60.04% of the total. The rats were treated with 40 mg/kg, 20 mg/kg, 10 mg/kg or 5 mg/kg BAPT, and 0.942 mg/kg loratadine and 0.5% gum tragacanth were used as positive and negative controls, respectively. The frequency of nose rubbing and sneezing was observed, the number of eosinophils infiltrating into the nasal tissue was counted, and serum levels of IL-4 and histamine were determined by ELISA. The results showed that BAPT had a beneficial effect on allergic rhinitis in ovalbumin-sensitized Wistar rats, which was evidenced by a significant decrease in the frequency of sneezing, the number of eosinophils infiltrating into the nasal tissue, and the serum levels of IL-4 and histamine. BAPT may therefore be a potential antiallergic drug.