Using principal component analysis and support vector machine to predict protein structural class for low-similarity sequences via PSSM

The accurate identification of protein structure class solely using extracted information from protein sequence is a complicated task in the current computational biology. Prediction of protein structural class for low-similarity sequences remains a challenging problem. In this study, the new computational method has been developed to predict protein structural class by fusing the sequence information and evolution information to represent a protein sample. To evaluate the performance of the proposed method, jackknife cross-validation tests are performed on two widely used benchmark data-sets, 1189 and 25PDB with sequence similarity lower than 40 and 25%, respectively. Comparison of our results with other methods shows that the proposed method by us is very promising and may provide a cost-effective alternative to predict protein structural class in particular for low-similarity data-sets.     

Enhanced sampling of molecular dynamics simulation of peptides and proteins by double coupling to thermal bath

Low sampling efficiency in conformational space is the well-known problem for conventional molecular dynamics. It greatly increases the difficulty for molecules to find the transition path to native state, and costs amount of CPU time. To accelerate the sampling, in this paper, we re-couple the critical degrees of freedom in the molecule to environment temperature, like dihedrals in generalized coordinates or nonhydrogen atoms in Cartesian coordinate. After applying to ALA dipeptide model, we find that this modified molecular dynamics greatly enhances the sampling behavior in the conformational space and provides more information about the state-to-state transition, while conventional molecular dynamics fails to do so. Moreover, from the results of 16 independent 100?ns simulations by the new method, it shows that trpzip2 has one-half chances to reach the naive state in all the trajectories, which is greatly higher than conventional molecular dynamics. Such an improvement would provide a potential way for searching the conformational space or predicting the most stable states of peptides and proteins.     

Molecular dynamics simulation on the effect of transition metal binding to the N-terminal fragment of amyloid-β

Abstract

We report molecular dynamics simulations of three possible adducts of Fe(II) to the N-terminal 1–16 fragments of the amyloid-β peptide, along with analogous simulations of Cu(II) and Zn(II) adducts. We find that multiple simulations from different starting points reach pseudo-equilibration within 100–300?ns, leading to over 900?ns of equilibrated trajectory data for each system. The specifics of the coordination modes for Fe(II) have only a weak effect on peptide secondary and tertiary structures, and we therefore compare one of these with analogous models of Cu(II) and Zn(II) complexes. All share broadly similar structural features, with mixture of coil, turn and bend in the N-terminal region and helical structure for residues 11–16. Within this overall pattern, subtle effects due to changes in metal are evident: Fe(II) complexes are more compact and are more likely to occupy bridge and ribbon regions of Ramachandran maps, while Cu(II) coordination leads to greater occupancy of the poly-proline region. Analysis of representative clusters in terms of molecular mechanics energy and atoms-in-molecules properties indicates similarity of four-coordinate Cu and Zn complexes, compared to five-coordinate Fe complex that exhibits lower stability and weaker metal–ligand bonding.

Communicated by Ramaswamy H. Sarma     

Expression of integrins α3β1 and α5β1 and GlcNAc β1,6 glycan branching influences metastatic melanoma cell migration on fibronectin

Acquisition of metastatic potential is accompanied by changes in cell surface N-glycosylation. One of the best-studied changes is increased expression of N-acetylglucosaminyltransferase V enzyme (GnT-V) and its products, β1,6-branched N-linked oligosaccharides, observed in the tumorigenesis of many cancers. In this study we demonstrate that during the transition from the vertical growth phase (VGP) (WM793 cell line) to the metastatic stage (WM1205Lu line), β1,6 glycosylation of melanoma cell surface proteins increases as a consequence of elevated expression of the GnT-V-encoding Mgat-5 gene. Treatment with swainsonine led to reduced cell motility on fibronectin in both cell lines; the effect was stronger in metastatic cells, probably due to the higher content of GlcNAc β1,6-branched glycans on the main fibronectin receptors – integrins α5β1 and α3β1. Our results show that GlcNAc β1,6 N-glycosylation of cell surface receptors, which increases with the aggressiveness of melanoma cells, is an important factor influencing melanoma cell migration.     

miR-181a–Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma

Although many researches have been undertaken to disclose the mechanisms of chemoresistance, the mechanisms remain unclear. The aim of this study is to elucidate the role of miR-181a–Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma (TSCC). We found that cisplatin-induced chemoresistance in TSCC cell lines underwent EMT (epithelial–mesenchymal transition) and was accompanied by enhancing metastatic potential (migration and invasion in vitro), miR-181a downregulation and Twist1 upregulation. Functional analyses indicated that miR-181a reversed chemoresistance, inhibited EMT and metastatic potential in TSCC cells. Twist1 was confirmed as a direct miR-181a target gene by luciferase reporter gene assays. Twist1 knockdown by siRNA led to a reversal of the chemoresistance, inhibited EMT and metastatic potential in TSCC cells. Our study demonstrates that miR-181a–Twist1 pathway may play an important role in the development of cisplatin-chemoresistance, with EMT and an increase the metastatic potential of TSCC cells.     

Impacts of inundation and drought on eukaryote biodiversity in semi‐arid floodplain soils

Floodplain ecosystems are characterized by alternating wet and dry phases and periodic inundation defines their ecological character. Climate change, river regulation and the construction of levees have substantially altered natural flooding and drying regimes worldwide with uncertain effects on key biotic groups. In southern Australia, we hypothesized that soil eukaryotic communities in climate change affected areas of a semi‐arid floodplain would transition towards comprising mainly dry‐soil specialist species with increasing drought severity. Here, we used 18S rRNA amplicon pyrosequencing to measure the eukaryote community composition in soils that had been depleted of water to varying degrees to confirm that reproducible transitional changes occur in eukaryotic biodiversity on this floodplain. Interflood community structures (3 years post‐flood) were dominated by persistent rather than either aquatic or dry‐specialist organisms. Only 2% of taxa were unique to dry locations by 8 years post‐flood, and 10% were restricted to wet locations (inundated a year to 2 weeks post‐flood). Almost half (48%) of the total soil biota were detected in both these environments. The discovery of a large suite of organisms able to survive nearly a decade of drought, and up to a year submerged supports the concept of inherent resilience of Australian semi‐arid floodplain soil communities under increasing pressure from climatic induced changes in water availability.     

Skull and limb morphology differentially track population history and environmental factors in the transition to agriculture in Europe

The Neolithic transition in Europe was a complex mosaic spatio-temporal process, involving both demic diffusion from the Near East and the cultural adoption of farming practices by indigenous hunter–gatherers. Previous analyses of Mesolithic hunter–gatherers and Early Neolithic farmers suggest that cranial shape variation preserves the population history signature of the Neolithic transition. However, the extent to which these same demographic processes are discernible in the postcranium is poorly understood. Here, for the first time, crania and postcranial elements from the same 11 prehistoric populations are analysed together in an internally consistent theoretical and methodological framework. Results show that while cranial shape reflects the population history differences between Mesolithic and Neolithic lineages, relative limb dimensions exhibit significant congruence with environmental variables such as latitude and temperature, even after controlling for geography and time. Also, overall limb size is found to be consistently larger in hunter–gatherers than farmers, suggesting a reduction in size related to factors other than thermoregulatory adaptation. Therefore, our results suggest that relative limb dimensions are not tracking the same demographic population history as the cranium, and point to the strong influence of climatic, dietary and behavioural factors in determining limb morphology, irrespective of underlying neutral demographic processes.     

Synthesis,antiproliferative and mitochondrial impairment activities of bis-alkyl-amino transplatinum complexes

A convenient synthetic route and the characterization of complexes trans-[PtCl₂(L)(PPh₃)] (L = Et₂NH (2), (PhCH₂)₂NH (3), (HOCH₂CH₂)₂NH) (4) are reported. The antiproliferative activity was evaluated on three human tumor cell lines. The investigation on the mechanism of action highlighted for the most active complex 4 the capacity to affect mitochondrial functions. In particular, both the induction of the mitochondrial permeability transition phenomenon and an aspecific membrane damage occurred, depending on concentration.