scholarly journals Rice protein models from the Nutritious Rice for the World Project

2016 ◽  
Author(s):  
Ling-Hong Hung ◽  
Ram Samudrala
Keyword(s):  
Protein Sequence ◽  
Structure Prediction ◽  
De Novo ◽  
Rice Protein ◽  
Large Sets ◽  
Small Proteins ◽  
The World ◽  
Protein Models ◽  
New Protein

AbstractBackgroundMany rice protein sequences are very different from the sequence of proteins with known structures. Homology modeling is not possible for many rice proteins. However, it is possible to use computational intensive de novo techniques to obtain protein models when the protein sequence cannot be mapped to a protein of known structure. The Nutritious Rice for the World project generated 10 billion models encompassing more than 60,000 small proteins and protein domains for the rice strains Oryza sativa and Oryza japonica.FindingsOver a period of 1.5 years, the volunteers of World Community Grid supported by IBM generated 10 billion candidate structures, a task that would have taken a single CPU on the order of 10 millennia. For each protein sequence, 5 top structures were chosen using a novel clustering methodology developed for analyzing large datasets. These are provided along with the entire set of 10 billion conformers.ConclusionsWe anticipate that the centroid models will be of use in visualizing and determining the role of rice proteins where the function is unknown. The entire set of conformers is unique in terms of size and that they were derived from sequences that lack detectable homologs. Large sets of de novo conformers are rare and we anticipate that this set will be useful for benchmarking and developing new protein structure prediction methodologies.

scholarly journals Discovery of novel community-relevant small proteins in a simplified human intestinal microbiome

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Hannes Petruschke ◽  
Christian Schori ◽  
Sebastian Canzler ◽  
Sarah Riesbeck ◽  
Anja Poehlein ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Intestinal Microbiota ◽  
De Novo ◽  
Bacterial Species ◽  
Intestinal Microbiome ◽  
Single Strain ◽  
Small Proteins ◽  
Human Intestinal Microbiota ◽  
Wide Range

Abstract Background The intestinal microbiota plays a crucial role in protecting the host from pathogenic microbes, modulating immunity and regulating metabolic processes. We studied the simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species with a particular focus on the discovery of novel small proteins with less than 100 amino acids (= sProteins), some of which may contribute to shape the simplified human intestinal microbiota. Although sProteins carry out a wide range of important functions, they are still often missed in genome annotations, and little is known about their structure and function in individual microbes and especially in microbial communities. Results We created a multi-species integrated proteogenomics search database (iPtgxDB) to enable a comprehensive identification of novel sProteins. Six of the eight SIHUMIx species, for which no complete genomes were available, were sequenced and de novo assembled. Several proteomics approaches including two earlier optimized sProtein enrichment strategies were applied to specifically increase the chances for novel sProtein discovery. The search of tandem mass spectrometry (MS/MS) data against the multi-species iPtgxDB enabled the identification of 31 novel sProteins, of which the expression of 30 was supported by metatranscriptomics data. Using synthetic peptides, we were able to validate the expression of 25 novel sProteins. The comparison of sProtein expression in each single strain versus a multi-species community cultivation showed that six of these sProteins were only identified in the SIHUMIx community indicating a potentially important role of sProteins in the organization of microbial communities. Two of these novel sProteins have a potential antimicrobial function. Metabolic modelling revealed that a third sProtein is located in a genomic region encoding several enzymes relevant for the community metabolism within SIHUMIx. Conclusions We outline an integrated experimental and bioinformatics workflow for the discovery of novel sProteins in a simplified intestinal model system that can be generically applied to other microbial communities. The further analysis of novel sProteins uniquely expressed in the SIHUMIx multi-species community is expected to enable new insights into the role of sProteins on the functionality of bacterial communities such as those of the human intestinal tract.

scholarly journals NAD+-Dependent Deacetylase Hst1p Controls Biosynthesis and Cellular NAD+ Levels in Saccharomyces cerevisiae

2003 ◽  
Vol 23 (19) ◽  
pp. 7044-7054 ◽  
Author(s):  
Antonio Bedalov ◽  
Maki Hirao ◽  
Jeffrey Posakony ◽  
Melisa Nelson ◽  
Julian A. Simon
Keyword(s):  
De Novo ◽  
Critical Role ◽  
Salvage Pathway ◽  
De Novo Synthesis ◽  
Array Analysis ◽  
Binding Partner ◽  
Dependent Protein ◽  
New Protein

ABSTRACT Nicotine adenine dinucleotide (NAD+) performs key roles in electron transport reactions, as a substrate for poly(ADP-ribose) polymerase and NAD+-dependent protein deacetylases. In the latter two processes, NAD+ is consumed and converted to ADP-ribose and nicotinamide. NAD+ levels can be maintained by regeneration of NAD+ from nicotinamide via a salvage pathway or by de novo synthesis of NAD+ from tryptophan. Both pathways are conserved from yeast to humans. We describe a critical role of the NAD+-dependent deacetylase Hst1p as a sensor of NAD+ levels and regulator of NAD+ biosynthesis. Using transcript arrays, we show that low NAD+ states specifically induce the de novo NAD+ biosynthesis genes while the genes in the salvage pathway remain unaffected. The NAD+-dependent deacetylase activity of Hst1p represses de novo NAD+ biosynthesis genes in the absence of new protein synthesis, suggesting a direct effect. The known Hst1p binding partner, Sum1p, is present at promoters of highly inducible NAD+ biosynthesis genes. The removal of HST1-mediated repression of the NAD+ de novo biosynthesis pathway leads to increased cellular NAD+ levels. Transcript array analysis shows that reduction in cellular NAD+ levels preferentially affects Hst1p-regulated genes in comparison to genes regulated with other NAD+-dependent deacetylases (Sir2p, Hst2p, Hst3p, and Hst4p). In vitro experiments demonstrate that Hst1p has relatively low affinity toward NAD+ in comparison to other NAD+-dependent enzymes. These findings suggest that Hst1p serves as a cellular NAD+ sensor that monitors and regulates cellular NAD+ levels.

Increasing the accuracy of protein loop structure prediction with evolutionary constraints

2018 ◽  
Vol 35 (15) ◽  
pp. 2585-2592 ◽  
Author(s):  
Claire Marks ◽  
Charlotte M Deane
Keyword(s):  
Structure Prediction ◽  
De Novo ◽  
Conformational Space ◽  
Supplementary Information ◽  
Evolutionary Constraints ◽  
Final Model ◽  
Loop Conformations ◽  
Loop Regions ◽  
Accuracy Of Prediction ◽  
Protein Models

Abstract Motivation Accurate prediction of loop structures remains challenging. This is especially true for long loops where the large conformational space and limited coverage of experimentally determined structures often leads to low accuracy. Co-evolutionary contact predictors, which provide information about the proximity of pairs of residues, have been used to improve whole-protein models generated through de novo techniques. Here we investigate whether these evolutionary constraints can enhance the prediction of long loop structures. Results As a first stage, we assess the accuracy of predicted contacts that involve loop regions. We find that these are less accurate than contacts in general. We also observe that some incorrectly predicted contacts can be identified as they are never satisfied in any of our generated loop conformations. We examined two different strategies for incorporating contacts, and on a test set of long loops (10 residues or more), both approaches improve the accuracy of prediction. For a set of 135 loops, contacts were predicted and hence our methods were applicable in 97 cases. Both strategies result in an increase in the proportion of near-native decoys in the ensemble, leading to more accurate predictions and in some cases improving the root-mean-square deviation of the final model by more than 3 Å. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals The dual role of fragments in fragment-assembly methods for de novo protein structure prediction

2011 ◽  
Vol 80 (2) ◽  
pp. 490-504 ◽  
Author(s):  
Julia Handl ◽  
Joshua Knowles ◽  
Robert Vernon ◽  
David Baker ◽  
Simon C. Lovell
Keyword(s):  
Protein Structure ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
De Novo ◽  
Dual Role ◽  
Fragment Assembly

Posttransplant CMV infection and the role of immunosuppression (Sponsor: Novartis Pharma GmbH, Nürnberg)

2016 ◽  
Vol 04 (01) ◽  
pp. 4-10
Keyword(s):  
Lower Incidence ◽  
Paradigm Shift ◽  
Mtor Inhibitor ◽  
De Novo ◽  
Expert Panel ◽  
Risk Of Infection ◽  
Cmv Infection ◽  
Expert Meeting ◽  
Selection Of

AbstractImmunosuppression permits graft survival after transplantation and consequently a longer and better life. On the other hand, it increases the risk of infection, for instance with cytomegalovirus (CMV). However, the various available immunosuppressive therapies differ in this regard. One of the first clinical trials using de novo everolimus after kidney transplantation [1] already revealed a considerably lower incidence of CMV infection in the everolimus arms than in the mycophenolate mofetil (MMF) arm. This result was repeatedly confirmed in later studies [2–4]. Everolimus is now considered a substance with antiviral properties. This article is based on the expert meeting “Posttransplant CMV infection and the role of immunosuppression”. The expert panel called for a paradigm shift: In a CMV prevention strategy the targeted selection of the immunosuppressive therapy is also a key element. For patients with elevated risk of CMV, mTOR inhibitor-based immunosuppression is advantageous as it is associated with a significantly lower incidence of CMV events.

The essence and causes of the spiritual and moral decline of mankind in the XX century

1998 ◽  
pp. 124-127
Author(s):  
V. Tolkachenko
Keyword(s):  
Well Being ◽  
Religious Institutions ◽  
Social Force ◽  
The World ◽  
Role Of Religion

One of the most important reasons for such a clearly distressed state of society was the decline of religion as a social force, the external manifestation of which is the weakening of religious institutions. "Religion," Baha'u'llah writes, "is the greatest of all means of establishing order in the world to the universal satisfaction of those who live in it." The weakening of the foundations of religion strengthened the ranks of ignoramuses, gave them impudence and arrogance. "I truly say that everything that belittles the supreme role of religion opens way for the revelry of maliciousness, inevitably leading to anarchy. " In another Tablet, He says: "Religion is a radiant light and an impregnable fortress that ensures the safety and well-being of the peoples of the world, for God-fearing induces man to adhere to the good and to reject all evil." Blink the light of religion, and chaos and distemper will set in, the radiance of justice, justice, tranquility and peace. "

The problem of periodization of the history of religion

1997 ◽  
pp. 3-8
Author(s):  
Borys Lobovyk
Keyword(s):  
Religious Studies ◽  
Human Being ◽  
Religious Development ◽  
History Of Religion ◽  
The Social ◽  
The World ◽  
History Of ◽  
Role Of Religion

An important problem of religious studies, the history of religion as a branch of knowledge is the periodization process of the development of religious phenomenon. It is precisely here, as in focus, that the question of the essence and meaning of the religious development of the human being of the world, the origin of beliefs and cult, the reasons for the changes in them, the place and role of religion in the social and spiritual process, etc., are converging.

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