APIS: accurate prediction of hot spots in protein interfaces by combining protrusion index with solvent accessibility

<p>Abstract</p> <p>Background</p> <p>It is well known that most of the binding free energy of protein interaction is contributed by a few key hot spot residues. These residues are crucial for understanding the function of proteins and studying their interactions. Experimental hot spots detection methods such as alanine scanning mutagenesis are not applicable on a large scale since they are time consuming and expensive. Therefore, reliable and efficient computational methods for identifying hot spots are greatly desired and urgently required.</p> <p>Results</p> <p>In this work, we introduce an efficient approach that uses support vector machine (SVM) to predict hot spot residues in protein interfaces. We systematically investigate a wide variety of 62 features from a combination of protein sequence and structure information. Then, to remove redundant and irrelevant features and improve the prediction performance, feature selection is employed using the F-score method. Based on the selected features, nine individual-feature based predictors are developed to identify hot spots using SVMs. Furthermore, a new ensemble classifier, namely APIS (A combined model based on Protrusion Index and Solvent accessibility), is developed to further improve the prediction accuracy. The results on two benchmark datasets, ASEdb and BID, show that this proposed method yields significantly better prediction accuracy than those previously published in the literature. In addition, we also demonstrate the predictive power of our proposed method by modelling two protein complexes: the calmodulin/myosin light chain kinase complex and the heat shock locus gene products U and V complex, which indicate that our method can identify more hot spots in these two complexes compared with other state-of-the-art methods.</p> <p>Conclusion</p> <p>We have developed an accurate prediction model for hot spot residues, given the structure of a protein complex. A major contribution of this study is to propose several new features based on the protrusion index of amino acid residues, which has been shown to significantly improve the prediction performance of hot spots. Moreover, we identify a compact and useful feature subset that has an important implication for identifying hot spot residues. Our results indicate that these features are more effective than the conventional evolutionary conservation, pairwise residue potentials and other traditional features considered previously, and that the combination of our and traditional features may support the creation of a discriminative feature set for efficient prediction of hot spot residues. The data and source code are available on web site <url>http://home.ustc.edu.cn/~jfxia/hotspot.html</url>.</p

Generalized uncertainty principle and correction value to the black hole entropy

Recently, there has been much attention devoted to resolving the quantum corrections to the Bekenstein-Hawking entropy of the black hole. In particular, many researchers have expressed a vested interest in the coefficient of the logarithmic term of the black hole entropy correction term. In this paper, we calculate the correction value of the black hole entropy by utilizing the generalized uncertainty principle and obtain the correction term caused by the generalized uncertainty principle. Because in our calculation we think that the Bekenstein-Hawking area theorem is still valid after considering the generalized uncertainty principle, we derive that the coefficient of the logarithmic term of the black hole entropy correction term is negative. This result is different from the known result at present. Our method is valid not only for single horizon spacetime but also for double horizons spacetime. In the whole process, the physics idea is clear and calculation is simple. It offers a new way for studying the condition that Bekenstein-Hawking area theorem is valid

Flat tie-line power scheduling control of grid-connected hybrid microgrids

In future active distribution networks (ADNs), microgrids (MGs) may have the possibility to control the power dispatched to the ADN by coordinating the output power of their multiple renewable generation units and energy storage units (ESUs). In this way, each MG may support the active distribution network, while promoting the penetration of renewable energy sources in a rational way. In this paper, we propose a tie-line power flow control of a hybrid MG, including photovoltaic (PV) generator, small wind turbines (WT), and ESUs. Firstly, the structure of the hybrid PV/WT/ESU MG is presented. In this power architecture, the battery is directly connected to the PV side through a DC/DC converter, thus reducing the number of conversions. Secondly, a hierarchical control is proposed to coordinate all those elements of the MG, making the tie-line power flow constant for a period of time, e.g. 15 min. Also, a method to calculate the tie-line power flow to be exchanged between the MG and the ADN is explored, and a power ramp rate is given between different dispatch intervals. Finally, a simulation model of the hybrid MG is built and tested. Simulation results show that the proposed hierarchical control strategy can select the proper operational mode and achieve seamless transfer between different modes. It also presents power curtailment functionality when the difference between the WT/PV output power and tie-line exchanged power flow is too large.</p

Epigenetics in ovarian cancer: premise, properties, and perspectives.

Malignant ovarian tumors bear the highest mortality rate among all gynecological cancers. Both late tumor diagnosis and tolerance to available chemical therapy increase patient mortality. Therefore, it is both urgent and important to identify biomarkers facilitating early identification and novel agents preventing recurrence. Accumulating evidence demonstrates that epigenetic aberrations (particularly histone modifications) are crucial in tumor initiation and development. Histone acetylation and methylation are respectively regulated by acetyltransferases-deacetylases and methyltransferases-demethylases, both of which are implicated in ovarian cancer pathogenesis. In this review, we summarize the most recent discoveries pertaining to ovarian cancer development arising from the imbalance of histone acetylation and methylation, and provide insight into novel therapeutic interventions for the treatment of ovarian carcinoma

Energy Chaos Characteristic Evolution Analysis of Sandstones during Multilevel Unloading Subject to Different Confining Pressures

AbstractIn this study, multilevel and conventional unloading triaxial compression tests under different confining pressures are separately carried out to systematically reveal the deformation, energy evolution, and fracture characteristics of sandstone samples. Results show that under the multilevel unloading condition, the increase of the initial confining pressure has a more obvious inhibitory effect on the radial strain of sandstone, and the samples can fully exhibit elastic deformation and partial plastic deformation, showing obvious plastic characteristics. The radial energy growth factor is more sensitive than the axial energy growth factor during the process of confining pressure unloading, and the larger the initial confining pressure, the earlier the period-doubling bifurcation region and chaotic region are reached. To better understand the deformation and failure process of rock during engineering excavation, it is necessary to establish a constitutive relation describing the mechanical properties of rock. The three-step failure mode also proves that there are tensile and shear fractures in sandstone samples, in which the effects of tensile stress and shear stress are more or less interdependent in the failure process. It can be seen that multilevel unloading makes the energy conversion more adequate and reduces the sudden release of energy when the rock fails, reducing the possibility of rockburst and making the excavation unloading process safer. This will deepen the understanding of rock failure behavior and contribute to the better application of energy characteristics to relevant engineering practices

Immunosuppressive effect of voacamine from Voacanga africana Stapf based on SPRi experiment

Purpose: To investigate the affinity of a bis-indole alkaloid - voacamine from Voacanga Africana Stapf for IL-2Rα - and its immunosuppressive effect on concanavalin A-induced T cell proliferation and lipopolysaccharide -induced B cell proliferation in vitro. Methods: Surface plasmon resonance imaging (SPRi) was used to screen the target protein of voacamine, while CCK-8 kit was used to evaluate cytotoxicity. Mitogen-induced proliferation assay was carried out to assess the inhibitory effect of voacamine on Con A-induced T cell proliferation and LPSinduced B cell proliferation. The binding characteristics of voacamine were investigated using a binding model with IL-2Rα constructed based on molecular docking simulation. Results: Voacamine had a high-affinity for IL-2Rα with an equilibrium dissociation constant (KD) of 1.85×10-8 M. Cytotoxicity data showed that voacamine did not exhibit cytotoxicity at concentrations lower than 0.32 µM. However, it exerted significant immunosuppressive effect on B cells at a lower concentration, but had no influence on proliferation of T cells. Autodock results indicate that voacamine has a good interaction with the enzyme active site. Conclusion: Voacamine and its analogues exert influence on the immune system

Gene therapy for C-26 colon cancer using heparin-polyethyleneimine nanoparticle-mediated survivin T34A

Ling Zhang1,*, Xiang Gao1,2,*, Ke Men1, BiLan Wang1, Shuang Zhang1, Jinfeng Qiu1, Meijuan Huang1, MaLing Gou1, Ning Huang2, ZhiYong Qian1, Xia Zhao1, YuQuan Wei11State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, 2Department of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, People&amp;rsquo;s Republic of China*These authors contributed equally to this workBackground: Gene therapy provides a novel method for the prevention and treatment of cancer, but the clinical application of gene therapy is restricted, mainly because of the absence of an efficient and safe gene delivery system. Recently, we developed a novel nonviral gene carrier, ie, heparin-polyethyleneimine (HPEI) nanoparticles for this purpose.Methods and results: HPEI nanoparticles were used to deliver plasmid-expressing mouse survivin-T34A (ms-T34A) to treat C-26 carcinoma in vitro and in vivo. According to the in vitro studies, HPEI nanoparticles could efficiently transfect the pGFP report gene into C-26 cells, with a transfection efficiency of 30.5% &amp;plusmn; 2%. Moreover, HPEI nanoparticle-mediated ms-T34A could efficiently inhibit the proliferation of C-26 cells by induction of apoptosis in vitro. Based on the in vivo studies, HPEI nanoparticles could transfect the Lac-Z report gene into C-26 cells in vivo. Intratumoral injection of HPEI nanoparticle-mediated ms-T34A significantly inhibited growth of subcutaneous C-26 carcinoma in vivo by induction of apoptosis and inhibition of angiogenesis.Conclusion: This research suggests that HPEI nanoparticle-mediated ms-T34A may have a promising role in C-26 colon carcinoma therapy.Keywords: gene therapy, mouse survivin-T34A, colon cancer, polyethyleneimine, nanoparticles, cancer therap