VPMCD: variable interaction modeling approach for class discrimination in biological systems

Data classification algorithms applied for class prediction in computational biology literature are data specific and have shown varying degrees of performance. Different classes cannot be distinguished solely based on interclass distances or decision boundaries. We propose that inter-relations among the features be exploited for separating observations into specific classes. A new variable predictive model based class discrimination (VPMCD) method is described here. Three well established and proven data sets of varying statistical and biological significance are utilized as benchmark. The performance of the new method is compared with advanced classification algorithms. The new method performs better during different tests and shows higher stability and robustness. The VPMCD is observed to be a potentially strong classification approach and can be effectively extended to other data mining applications involving biological systems.     

Permeation mechanism of a two-state potassium channel

A two-state hopping model was proposed to study the permeation of ion channel. The Nernst equation in equilibrium and the Michaelis-Menten relation in steady state were derived from the two-state kinetic model. The current-voltage relationship obtained in the symmetrical solutions case was linear when the applied potential was less than 100 mV, which met Ohm’s law. The conductance-concentration relationship exhibited the saturation property. Moreover, the characteristic time reaching the steady state of the KcsA channel was also discussed. Translated from Acta Biophysica Sinica, 2005, 21(4): 289–294 [译自: 生物物理学报]     

On the relative stabilities of the alkali cations 222 cryptates in the gas phase and in water-methanol solution

The relative stabilities of the alkali [M ⊂ 222]⁺ cryptates (M = Na, K, Rb and Cs) in the gas phase and in solution (80:20 v/v methanol:water mixture) at 298 K, are computed using a combination of ab initio quantum-chemical calculations (HF/6-31G and MP2/6-31+G*//HF/6-31+G*) and explicit-solvent Monte Carlo free-energy simulations. The results suggest that the relative stabilities of the cryptates in solution are due to a combination of steric effects (compression of large ions within the cryptand cavity), electronic effects (delocalization of the ionic charge onto the cryptand atoms) and solvent effects (dominantly the ionic dessolvation penalty). Thus, the relative stabilities in solution cannot be rationalized solely on the basis of a simple match or mismatch between the ionic radius and the cryptand cavity size as has been suggested previously. For example, although the [K ⊂ 222]⁺ cryptate is found to be the most stable in solution, in agreement with experimental data, it is the [Na ⊂ 222]⁺ cryptate that is the most stable in the gas phase. The present results provide further support to the notion that the solvent in which supramolecules are dissolved plays a key role in modulating molecular recognition processes. Figure Alkali cryptates [M ⊂ 222]+ (M = Na, K, Rb and Cs) relative stabilities in gas and methanol:water solution: solvent effects and molecular recognition

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Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Mycobacterial PE_PGRS proteins contain calcium-binding motifs with parallel beta-roll folds

The PE_PGRS family of proteins unique to mycobacteria is demonstrated to contain multiple calcium-binding and glycine-rich sequence motifs GGXGXD/NXUX. This sequence repeat constitutes a calcium-binding parallel beta-roll or parallel beta-helix structure and is found in RTX toxins secreted by many Gram-negative bacteria. It is predicted that the highly homologous PE PGRS proteins containing multiple copies of the nona-peptide motif could fold into similar calcium-binding structures. The implication of the predicted calcium-binding property of PE PGRS proteins in the light of macrophage-pathogen interaction and pathogenesis is presented.     

Exploring the antimalarial potential of the methoxy-thiazinoquinone scaffold: Identification of a new lead candidate

A small library of antiplasmodial methoxy-thiazinoquinones, rationally designed on the model of the previously identified hit 1, has been prepared by a simple and inexpensive procedure. The synthetic derivatives have been subjected to in vitro pharmacological screening, including antiplasmodial and toxicity assays. These studies afforded a new lead candidate, compound 9, endowed with higher antiplasmodial potency compared to 1, a good selectivity index when tested against a panel of mammalian cells, no toxicity against RBCs, a synergistic antiplasmodial action in combination with dihydroartemisinin, and a promising inhibitory activity on stage V gametocyte growth. Computational studies provided useful insights into the structural requirements needed for the antiplasmodial activity of thiazinoquinone compounds and on their putative mechanism of action.     

Scalable remote homology detection and fold recognition in massive protein networks

The global connectivities in very large protein similarity networks contain traces of evolution among the proteins for detecting protein remote evolutionary relations or structural similarities. To investigate how well a protein network captures the evolutionary information, a key limitation is the intensive computation of pairwise sequence similarities needed to construct very large protein networks. In this article, we introduce label propagation on low-rank kernel approximation (LP-LOKA) for searching massively large protein networks. LP-LOKA propagates initial protein similarities in a low-rank graph by Nyström approximation without computing all pairwise similarities. With scalable parallel implementations based on distributed-memory using message-passing interface and Apache-Hadoop/Spark on cloud, LP-LOKA can search protein networks with one million proteins or more. In the experiments on Swiss-Prot/ADDA/CASP data, LP-LOKA significantly improved protein ranking over the widely used HMM-HMM or profile-sequence alignment methods utilizing large protein networks. It was observed that the larger the protein similarity network, the better the performance, especially on relatively small protein superfamilies and folds. The results suggest that computing massively large protein network is necessary to meet the growing need of annotating proteins from newly sequenced species and LP-LOKA is both scalable and accurate for searching massively large protein networks.     

烟粉虱对几种常见蔬菜寄主的取食选择性

在多种蔬菜寄主同时存在的情况下,烟粉虱对寄主的选择性和嗜好性排序为:黄瓜>节瓜,番茄,菜豆>芥蓝,茄子>甘蓝,苦瓜。     

Principles of selective inactivation of a viral genome. Comparative kinetic study of modification of the viral RNA and model protein with oligoaziridines

Comparative kinetic analysis of inactivation of bacteriophage MS2 infectivity and aminoalkylation of a model protein (trypsin inhibitor) with oligoaziridines was performed in order to evaluate the selectivity of viral RNA modification with oligocationic reagents. The transition from ethyleneimine monomer to di-, tri-, and tetramer leads to a sharp increase in the rate constant of infectivity inactivation, whereas the rate constant of protein modification changes insignificantly. The selectivity coefficient of the phage RNA aminoalkylation relative to trypsin inhibitor modification increases in this series by more than an order of magnitude. This effect is probably associated with the strengthening of the reagent binding to the nucleic acid, which implies a reaction mechanism that involves the formation of a reactive intermediate. The latter might be an electrostatic complex of the oligocationic reagent and RNA, the only polyanion in the virion. A pronounced decrease in the rate constant of infectivity inactivation in the presence of multiply charged anions (in phosphate buffer) and a biogenic polyamine (spermine) favors this hypothesis. Increasing the reaction temperature increases the rate constant of infectivity inactivation and decreases selectivity of the viral RNA modification.     

Single channel properties of P2X2 purinoceptors

The single channel properties of cloned P2X2 purinoceptors expressed in human embryonic kidney (HEK) 293 cells and Xenopus oocytes were studied in outside-out patches. The mean single channel current-voltage relationship exhibited inward rectification in symmetric solutions with a chord conductance of approximately 30 pS at -100 mV in 145 mM NaCl. The channel open state exhibited fast flickering with significant power beyond 10 kHz. Conformational changes, not ionic blockade, appeared responsible for the flickering. The equilibrium constant of Na+ binding in the pore was approximately 150 mM at 0 mV and voltage dependent. The binding site appeared to be approximately 0.2 of the electrical distance from the extracellular surface. The mean channel current and the excess noise had the selectivity: K+ > Rb+ > Cs+ > Na+ > Li+. ATP increased the probability of being open (Po) to a maximum of 0.6 with an EC50 of 11.2 microM and a Hill coefficient of 2.3. Lowering extracellular pH enhanced the apparent affinity of the channel for ATP with a pKa of approximately 7.9, but did not cause a proton block of the open channel. High pH slowed the rise time to steps of ATP without affecting the fall time. The mean single channel amplitude was independent of pH, but the excess noise increased with decreasing pH. Kinetic analysis showed that ATP shortened the mean closed time but did not affect the mean open time. Maximum likelihood kinetic fitting of idealized single channel currents at different ATP concentrations produced a model with four sequential closed states (three binding steps) branching to two open states that converged on a final closed state. The ATP association rates increased with the sequential binding of ATP showing that the binding sites are not independent, but positively cooperative. Partially liganded channels do not appear to open. The predicted Po vs. ATP concentration closely matches the single channel current dose-response curve.     

Flowers in tri-trophic systems: mechanisms allowing selective exploitation by insect natural enemies for conservation biological control

Many insects have coevolved with certain angiosperm taxa to act as pollinators. However, the nectar and pollen from such flowers is also widely fed upon by other insects, including entomophagous species. Conservation biological control seeks to maximise the impact of these natural enemies on crop pests by enhancing availability of nectar and pollen-rich plants in agroecosystems. A risk with this approach is that pests may also benefit from the food resource. We show that the flowers of some plants (viz., buckwheat, Fagopyron esculentum Moench and dill, Anethum graveolens L.), and the extrafloral nectaries of faba bean (Vicia faba L.) benefit both Copidosoma koehleri Blanchard (Hymenoptera: Encyrtidae) and its host, the potato pest, Phthorimaea operculella Zeller (Lepidoptera: Gelechiidae). In contrast, phacelia (Phacelia tanacetifolia Benth) and nasturtium (Tropaeoleum majus L.) benefited only the parasitoid. When adult moths of P. operculella were caged with flowers of phacelia or nasturtium, longevity of males and females, egg laying life, fecundity, average oviposition rate, and number of eggs in ovaries at death were no greater than in the control treatment with access to shoots without flowers plus water. All the foregoing measures were increased compared to the control when the moths were allowed access to dill, buckwheat or faba bean extrafloral nectaries. Such selectivity has the potential to make the use of floral resources in conservation biological control more strategic. We present morphometric and observational evidence to illustrate how such mechanisms may operate.