Prediction of protein-binding areas by small-world residue networks and application to docking

<p>Abstract</p> <p>Background</p> <p>Protein-protein interactions are involved in most cellular processes, and their detailed physico-chemical and structural characterization is needed in order to understand their function at the molecular level. In-silico docking tools can complement experimental techniques, providing three-dimensional structural models of such interactions at atomic resolution. In several recent studies, protein structures have been modeled as networks (or graphs), where the nodes represent residues and the connecting edges their interactions. From such networks, it is possible to calculate different topology-based values for each of the nodes, and to identify protein regions with high centrality scores, which are known to positively correlate with key functional residues, hot spots, and protein-protein interfaces.</p> <p>Results</p> <p>Here we show that this correlation can be efficiently used for the scoring of rigid-body docking poses. When integrated into the pyDock energy-based docking method, the new combined scoring function significantly improved the results of the individual components as shown on a standard docking benchmark. This improvement was particularly remarkable for specific protein complexes, depending on the shape, size, type, or flexibility of the proteins involved.</p> <p>Conclusions</p> <p>The network-based representation of protein structures can be used to identify protein-protein binding regions and to efficiently score docking poses, complementing energy-based approaches.</p

Comparative analysis of fungal protein kinases and associated domains

<p>Abstract</p> <p>Background</p> <p>Protein phosphorylation is responsible for a large portion of the regulatory functions of eukaryotic cells. Although the list of sequenced genomes of filamentous fungi has grown rapidly, the kinomes of recently sequenced species have not yet been studied in detail. The objective of this study is to apply a comparative analysis of the kinase distribution in different fungal phyla, and to explore its relevance to understanding the evolution of fungi and their taxonomic classification. We have analyzed in detail 12 subgroups of kinases and their distribution over 30 species, as well as their potential use as a classifier for members of the fungal kingdom.</p> <p>Results</p> <p>Our findings show that despite the similarity of the kinase distribution in all fungi, their domain distributions and kinome density can potentially be used to classify them and give insight into their evolutionary origin. In general, we found that the overall representation of kinase groups is similar across fungal genomes, the only exception being a large number of tyrosine kinase-like (TKL) kinases predicted in <it>Laccaria bicolor</it>. This unexpected finding underscores the need to continue to sequence fungal genomes, since many species or lineage-specific properties may remain to be discovered. Furthermore, we found that the domain organization significantly varies between the fungal species. Our results suggest that protein kinases and their functional domains strongly reflect fungal taxonomy.</p> <p>Conclusions</p> <p>Comparison of the predicted kinomes of sequenced fungi suggests essential signaling functions common to all species, but also specific adaptations of the signal transduction networks to particular species.</p

Upper and lower bounds on the mean square radius and criteria for occurrence of quantum halo states

In the context of non-relativistic quantum mechanics, we obtain several upper and lower limits on the mean square radius applicable to systems composed by two-body bound by a central potential. A lower limit on the mean square radius is used to obtain a simple criteria for the occurrence of S-wave quantum halo sates.Comment: 12 pages, 2 figure

Sufficient conditions for the existence of bound states in a central potential

We show how a large class of sufficient conditions for the existence of bound states, in non-positive central potentials, can be constructed. These sufficient conditions yield upper limits on the critical value, $g_{\rm{c}}^{(\ell)}$, of the coupling constant (strength), $g$, of the potential, $V(r)=-g v(r)$, for which a first $\ell$-wave bound state appears. These upper limits are significantly more stringent than hitherto known results.Comment: 7 page

ON ORBIT DEPLOYMENT OF THE EU:CROPIS SOLAR PANEL BY GFRP TAPE SPRING HINGES

Eu:CROPIS is a compact satellite featuring a biological payload. The Satellite was launched on December 3rd 2018. The cylindrical Satellite of 1m diameter has four deployable panels for power generation. Those panels are connected to the main structure by glass fibre reinforced polymer (GFRP) tape spring hinges. The hinges, comparable to curved metallic measuring tapes, have elastic energy stored when flattened and folded and thus deploy the panels by simply unfolding. When unfolded the hinges snap into their original shape and support the panels with considerable stiffness. No friction or mechanical locking is involved in the deploying process. The presented paper focuses on the practical handling of the hinges and the mechanisms during the final integration and the deployment process. The integration of the panels requires some special consideration. The hinges are not able to support the panels under gravity. The release mechanisms only work at a correct positioning of the panels. The measures taken to ensure the integrity and functionality of the hinges and mechanisms are described and examples are given for a correct and a false outcome. The separation is done by breaking a bolt with a heated bushing from shape memory alloy. Though reliable the separation cannot be timed down to the second and there is no direct feedback of the separation. To prevent an uneven opening of the panels several on orbit pre-tests are performed to ensure the functionality of the mechanisms for the actual deployment. At the actual separation the heating is monitored to ensure that all mechanisms are activated and the separation is working as proposed. Furthermore, a method was developed to detect the successful breaking of the bolts by use of the heating temperature data. The paper describes these checks and surveillance methods. As not all things go as planned some decisions were to be made before and at panel deployment. Also, the unfolding of the hinges was slower than during the on ground. Tests were made to simulate and understand the on-orbit behaviour. Lessons learned for further use of the mechanisms are presented

Upper and lower limits on the number of bound states in a central potential

In a recent paper new upper and lower limits were given, in the context of the Schr\"{o}dinger or Klein-Gordon equations, for the number $N_{0}$ of S-wave bound states possessed by a monotonically nondecreasing central potential vanishing at infinity. In this paper these results are extended to the number $N_{\ell}$ of bound states for the $\ell$-th partial wave, and results are also obtained for potentials that are not monotonic and even somewhere positive. New results are also obtained for the case treated previously, including the remarkably neat \textit{lower} limit $N_{\ell}\geq \{\{[\sigma /(2\ell+1)+1]/2\}\}$ with $V(r)| ^{1/2}]$ (valid in the Schr\"{o}dinger case, for a class of potentials that includes the monotonically nondecreasing ones), entailing the following \textit{lower} limit for the total number $N$ of bound states possessed by a monotonically nondecreasing central potential vanishing at infinity: N\geq \{\{(\sigma+1)/2\}\} {(\sigma+3)/2\} \}/2 (here the double braces denote of course the integer part).Comment: 44 pages, 5 figure

Necessary and sufficient conditions for existence of bound states in a central potential

We obtain, using the Birman-Schwinger method, a series of necessary conditions for the existence of at least one bound state applicable to arbitrary central potentials in the context of nonrelativistic quantum mechanics. These conditions yield a monotonic series of lower limits on the "critical" value of the strength of the potential (for which a first bound state appears) which converges to the exact critical strength. We also obtain a sufficient condition for the existence of bound states in a central monotonic potential which yield an upper limit on the critical strength of the potential.Comment: 7 page

Intrinsically active MEK variants are differentially regulated by proteinases and phosphatases

MAPK/ERK kinase (MEK) 1/2 are central signaling proteins that serve as specificity determinants of the MAPK/ERK cascade. More than twenty activating mutations have been reported for MEK1/2, and many of them are known to cause diseases such as cancers, arteriovenous malformation and RASopathies. Changes in their intrinsic activity do not seem to correlate with the severity of the diseases. Here we studied four MEK1/2 mutations using biochemical and molecular dynamic methods. Although the studied mutants elevated the activating phosphorylation of MEK they had no effect on the stimulated ERK1/2 phosphorylation. Studying the regulatory mechanism that may explain this lack of effect, we found that one type of mutation affects MEK stability and two types of mutations demonstrate a reduced sensitivity to PP2A. Together, our results indicate that some MEK mutations exert their function not only by their elevated intrinsic activity, but also by modulation of regulatory elements such as protein stability or dephosphorylation.We would like to thanks Mrs. Shira Wexler for her help in producing Fig. 7F. This study was supported by grants from ISF to RS. RS is an incumbent of the Yale S. Lewine and Ella Miller Lewine professorial chair for cancer research. CP acknowledges Severo Ochoa grant (SEV-2015-0493) for financial support. FLG acknowledges EPSRC [grant no EP/P022138/1; EP/P011306/1; EP/M013898/1] for financial support. HecBioSim [EPSRC grant no EP/P022138/1], Archer, JADE, the Hartree Centre, the Barcelona Supercomputing Center and PRACE are acknowledged for computer time. JF-R acknowledges Spanish MICINN grant [number BIO2016-79930-R] for financial support.Peer ReviewedPostprint (published version

Microbial rhodopsins on leaf surfaces of terrestrial plants

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Environmental Microbiology 14 (2012): 140-146, doi:10.1111/j.1462-2920.2011.02554.x.The above-ground surfaces of terrestrial plants, the phyllosphere, comprise the main interface between the terrestrial biosphere and solar radiation. It is estimated to host up to 1026 microbial cells that may intercept part of the photon flux impinging on the leaves. Based on 454- pyrosequencing generated metagenome data, we report on the existence of diverse microbial rhodopsins in five distinct phyllospheres from tamarisk (Tamarix nilotica), soybean (Glycine max), Arabidopsis (Arabidopsis thaliana), clover (Trifolium repens) and rice (Oryza sativa). Our findings, for the first time describing microbial rhodopsins from non-aquatic habitats, point toward the potential coexistence of microbial rhodopsin-based phototrophy and plant chlorophyll-based photosynthesis, with the different pigments absorbing non-overlapping fractions of the light spectrum.This work was supported in part by a grant from Bridging the Rift Foundation (O.B. & S.B.), Israel Science Foundation grant 1203/06 (O.B.), the Gruss-Lipper Family Foundation at MBL (O.M.F., S.B. & A.F.P.), a US-Israel Binational Science Foundation grant 2006324 (S.B.), and DOE National Institutes of Health Grant R37GM27750, Department of Energy Grant DE-FG02-07ER15867, and endowed chair AU-0009 from the Robert A. Welch Foundation (J.L.S.)