scholarly journals Vermont: a multi-perspective visual interactive platform for mutational analysis

2017 ◽  
Author(s):  
Alexandre V Fassio ◽  
Pedro M Martins ◽  
Samuel da S Guimarães ◽  
Sócrates S A Junior ◽  
Vagner S Ribeiro ◽  
...  
Keyword(s):  
Protein Function ◽  
Visual Analytics ◽  
Large Scale ◽  
Mutational Analysis ◽  
Structural Parameters ◽  
Point Mutations ◽  
Huge Amount ◽  
Interactive Visualizations ◽  
And Function ◽  
The Impact

AbstractBackgroundA huge amount of data about genomes and sequence variation is available and continues to grow on a large scale, which makes experimentally characterizing these mutations infeasible regarding disease association and effects on protein structure and function. Therefore, reliable computational approaches are needed to support the understanding of mutations and their impacts. Here, we present VERMONT 2.0, a visual interactive platform that combines sequence and structural parameters with interactive visualizations to make the impact of protein point mutations more understandable.ResultsWe aimed to contribute a novel visual analytics oriented method to analyze and gain insight on the impact of protein point mutations. To assess the ability of VERMONT to do this, we visually examined a set of mutations that were experimentally characterized to determine if VERMONT could identify damaging mutations and why they can be considered so.ConclusionsVERMONT allowed us to understand mutations by interpreting position-specific structural and physicochemical properties. Additionally, we note some specific positions we believe have an impact on protein function/structure in the case of mutation.

scholarly journals Mutational Analysis of Cdc19p, a Schizosaccharomyces pombe MCM Protein

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1025-1041 ◽  
Author(s):  
Susan L Forsburg ◽  
Daniel A Sherman ◽  
Sabine Ottilie ◽  
J Randy Yasuda ◽  
Jeffrey A Hodson
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Protein Function ◽  
Mutational Analysis ◽  
Point Mutations ◽  
Wild Type ◽  
Genes Encoding ◽  
Mcm Proteins ◽  
And Function ◽  
Mutant Forms ◽  
Replication Initiator

The cdc19  + gene encodes an essential member of the MCM family of replication proteins in Schizosaccharomyces pombe. We have examined the structure and function of the Cdc19p protein using molecular and genetic approaches. We find that overproduction of wild-type Cdc19p in wild-type cells has no effect, but cdc19-P1 mutant cells do not tolerate elevated levels of other MCM proteins or overexpression of mutant forms of Cdc19p. We have found genetic interactions between cdc19  + and genes encoding subunits of DNA polymerase δ and the replication initiator cdc18  +. We have constructed a series of point mutations and sequence deletions throughout Cdc19p, which allow us to distinguish essential from nonessential regions of the protein. Not surprisingly, conserved residues in the MCM homology domain are required for protein function, but some residues outside the core homology domain are dispensable.

scholarly journals iProteinDB: an integrative database of Drosophila post-translational modifications

2018 ◽  
Author(s):  
Yanhui Hu ◽  
Richelle Sopko ◽  
Verena Chung ◽  
Romain A. Studer ◽  
Sean D. Landry ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Large Scale ◽  
Model Organisms ◽  
General Strategy ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Functional Sites ◽  
Evolutionarily Conserved ◽  
And Function

AbstractPost-translational modification (PTM) serves as a regulatory mechanism for protein function, influencing stability, protein interactions, activity and localization, and is critical in many signaling pathways. The best characterized PTM is phosphorylation, whereby a phosphate is added to an acceptor residue, commonly serine, threonine and tyrosine. As proteins are often phosphorylated at multiple sites, identifying those sites that are important for function is a challenging problem. Considering that many phosphorylation sites may be non-functional, prioritizing evolutionarily conserved phosphosites provides a general strategy to identify the putative functional sites with regards to regulation and function. To facilitate the identification of conserved phosphosites, we generated a large-scale phosphoproteomics dataset from Drosophila embryos collected from six closely-related species. We built iProteinDB (https://www.flyrnai.org/tools/iproteindb/), a resource integrating these data with other high-throughput PTM datasets, including vertebrates, and manually curated information for Drosophila. At iProteinDB, scientists can view the PTM landscape for any Drosophila protein and identify predicted functional phosphosites based on a comparative analysis of data from closely-related Drosophila species. Further, iProteinDB enables comparison of PTM data from Drosophila to that of orthologous proteins from other model organisms, including human, mouse, rat, Xenopus laevis, Danio rerio, and Caenorhabditis elegans.

scholarly journals Identification and Characterization of novel mutants of Nsp13 Protein among Indian SARS-CoV-2 isolates.

2021 ◽  
Author(s):  
Deepa Kumari ◽  
Namrata Kumari ◽  
Sudhir Kumar ◽  
Prabhat Kumar Sinha ◽  
Shivendra Kumar Shahi ◽  
...  
Keyword(s):  
B Cell ◽  
Protein Function ◽  
Protein Sequences ◽  
Structural Protein ◽  
Immunological Parameters ◽  
B Cell Epitopes ◽  
Global Challenge ◽  
Indian Isolates ◽  
And Function ◽  
The Impact

SARS-CoV-2, the causative agent of COVID-19 has mutated rapidly which enabled them to adapt and evade the immune system of the host. Emerging SARS-CoV-2 variants with crucial mutations pose a global challenge in context of therapeutic drugs and vaccines being developed globally. There are currently no specific therapeutics or vaccines available to combat SARS-CoV-2 devastation. In view of this, the current study aimed to identify and characterize the mutations found in the Nsp13 of SARS-CoV-2 in Indian isolates. Non-structural protein, Nsp13 protein sequences from Indian isolates were analyzed by comparing with the first reported Severe acute respiratory syndrome Corona Virus-2 (SARS-CoV-2) protein sequence from Wuhan, China. Out of 825 Nsp13 protein sequences, a total of 38 mutations were observed among Indian isolates. Our data show that mutations in Nsp13 at various positions (H164Y, A237T, T214I, C309Y, S236I, P419S, V305E, G54S, H290Y, P53S, A308Y, and A308Y) have a significant impact on the protein's stability and flexibility. Also, the impact of Nsp13 mutations on the protein function were predicted based on PROVEAN score that includes 15 mutants as neutral and 23 mutants as deleterious effect. Furthermore, B-cell epitopes contributed by Nsp13 were identified using various predictive immunoinformatic tools. Immunological Parameters of Nsp13 such as antigenicity, allergenicity and toxicity were evaluated to predict the potential B-cell epitopes. The predicted peptide sequences were correlated with the observed mutants. Our predicted data showed that there are seven high rank linear epitopes as well as 18 discontinuous B-cell epitopes based on immunoinformatic tools. Moreover, it was observed that out of total 38 identified mutations among Indian SARS-CoV-2 Nsp13 protein, four mutant residues at position 142 (E142), 245 (H245), 247 (V247) and 419 (P419) are localised in the predicted B cell epitopic region. Altogether, the results of the present in-silico study might help to understand the impact of the identified mutations in Nsp13 protein on its stability, flexibility and function.

scholarly journals Using AlphaFold to predict the impact of single mutations on protein stability and function

2021 ◽  
Author(s):  
Marina A Pak ◽  
Karina A Markhieva ◽  
Mariia S Novikova ◽  
Dmitry S Petrov ◽  
Ilya S Vorobyev ◽  
...  
Keyword(s):  
Protein Folding ◽  
Protein Stability ◽  
Structure Prediction ◽  
Large Scale ◽  
3D Structure ◽  
Three Dimensional ◽  
Single Mutation ◽  
Before And After ◽  
And Function ◽  
The Impact

AlphaFold changed the field of structural biology by achieving three-dimensional (3D) structure prediction from protein sequence at experimental quality. The astounding success even led to claims that the protein folding problem is "solved". However, protein folding problem is more than just structure prediction from sequence. Presently, it is unknown if the AlphaFold-triggered revolution could help to solve other problems related to protein folding. Here we assay the ability of AlphaFold to predict the impact of single mutations on protein stability (ΔΔG) and function. To study the question we extracted metrics from AlphaFold predictions before and after single mutation in a protein and correlated the predicted change with the experimentally known ΔΔG values. Additionally, we correlated the AlphaFold predictions on the impact of a single mutation on structure with a large scale dataset of single mutations in GFP with the experimentally assayed levels of fluorescence. We found a very weak or no correlation between AlphaFold output metrics and change of protein stability or fluorescence. Our results imply that AlphaFold cannot be immediately applied to other problems or applications in protein folding.

scholarly journals Molecular Biologist's Guide to Proteomics

2002 ◽  
Vol 66 (1) ◽  
pp. 39-63 ◽  
Author(s):  
Paul R. Graves ◽  
Timothy A. J. Haystead
Keyword(s):  
Posttranslational Modifications ◽  
Protein Function ◽  
Large Scale ◽  
Protein Identification ◽  
Functional Proteomics ◽  
Computer Algorithms ◽  
Large Scale Analysis ◽  
Proteomics Approach ◽  
And Function ◽  
Identification And Characterization

SUMMARY The emergence of proteomics, the large-scale analysis of proteins, has been inspired by the realization that the final product of a gene is inherently more complex and closer to function than the gene itself. Shortfalls in the ability of bioinformatics to predict both the existence and function of genes have also illustrated the need for protein analysis. Moreover, only through the study of proteins can posttranslational modifications be determined, which can profoundly affect protein function. Proteomics has been enabled by the accumulation of both DNA and protein sequence databases, improvements in mass spectrometry, and the development of computer algorithms for database searching. In this review, we describe why proteomics is important, how it is conducted, and how it can be applied to complement other existing technologies. We conclude that currently, the most practical application of proteomics is the analysis of target proteins as opposed to entire proteomes. This type of proteomics, referred to as functional proteomics, is always driven by a specific biological question. In this way, protein identification and characterization has a meaningful outcome. We discuss some of the advantages of a functional proteomics approach and provide examples of how different methodologies can be utilized to address a wide variety of biological problems.

scholarly journals Structural dynamics is a determinant of the functional significance of missense variants

2018 ◽  
Vol 115 (16) ◽  
pp. 4164-4169 ◽  
Author(s):  
Luca Ponzoni ◽  
Ivet Bahar
Keyword(s):  
Structural Dynamics ◽  
Protein Function ◽  
Biological Function ◽  
Point Mutations ◽  
Computational Tools ◽  
Missense Variants ◽  
Pathogenicity Prediction ◽  
Cancer Types ◽  
The Impact ◽  
Insight Into

Accurate evaluation of the effect of point mutations on protein function is essential to assessing the genesis and prognosis of many inherited diseases and cancer types. Currently, a wealth of computational tools has been developed for pathogenicity prediction. Two major types of data are used to this aim: sequence conservation/evolution and structural properties. Here, we demonstrate in a systematic way that another determinant of the functional impact of missense variants is the protein’s structural dynamics. Measurable improvement is shown in pathogenicity prediction by taking into consideration the dynamical context and implications of the mutation. Our study suggests that the class of dynamics descriptors introduced here may be used in conjunction with existing features to not only increase the prediction accuracy of the impact of variants on biological function, but also gain insight into the physical basis of the effect of missense variants.

scholarly journals Assessment of water quality and state of waterbasins of different types from characteristics of benthic animal communities

2016 ◽  
Vol 320 (3) ◽  
pp. 262-279
Author(s):  
E.V. Balushkina
Keyword(s):  
Water Quality ◽  
Primary Production ◽  
Large Scale ◽  
Structural Parameters ◽  
Benthic Communities ◽  
River Estuary ◽  
Neva River ◽  
Relationship Of ◽  
The Impact ◽  
Neva Bay

Studies on waterbasins of different type have shown the impact of eutrophication and pollution by toxic and organic matter on the structural and functional characteristics of zoobenthos. A major factor determining quantitative development of non-predatory zoobenthos in lakes is, undoubtedly, the level of development of primary producers. Relationship of zoobenthos biomass and primary production is particularly pronounced in shallow lakes. Analysis of relationship of zoobenthos with abiotic and biotic factors in shallow hyperhaline lakes of Crimea has shown that the most significant parameters determining the values of biomass of macrozoobenthos were salinity and primary production, second in significance were oxygen concentration and depth. The changes in structure and quantitative characteristics of benthic communities of the Neva River estuary occur under impact of a complex combination of organic and toxic pollution. For the assessment of water quality and state of ecosystem in the Neva River estuary we used IP' integrated index specially devised by us for water-bodies and watercourses of north-western Russia. It is based on structural parameters of zoobenthic communities and makes it possible to take into consideration pollution with toxic and organic substances. On average the water quality of the Neva Bay judging from IP' values was relatively stable during 1982–2014. It was assessed as “polluted” with exception for abnormality in 2006 (“polluted–dirty”) caused by large-scale dredging work. As a result of stronger pollution, species diversity of benthic animals in the Resort District of the eastern part of the Gulf of Finland is lower than in the Neva Bay.

scholarly journals Intra-individual methylomics detects the impact of early-life adversity

2018 ◽  
Author(s):  
Shan Jiang ◽  
Noriko Kamei ◽  
Jessica L. Bolton ◽  
Xinyi Ma ◽  
Hal S. Stern ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Fate ◽  
Early Life ◽  
Large Scale ◽  
Life Experience ◽  
Early Life Adversity ◽  
Health And Disease ◽  
Genetic And Environmental Factors ◽  
And Function ◽  
The Impact

AbstractGenetic and environmental factors interact during sensitive periods early in life to influence mental health and disease via epigenetic processes such as DNA methylation. However, it is not known if DNA methylation changes outside the brain provide an ‘epigenetic signature’ of early-life experiences. Here, we employed a novel intra-individual approach by testing DNA methylation from buccal cells of individual rats before and immediately after exposure to one week of typical or adverse life experience. We find that whereas inter-individual changes in DNA methylation reflect the effect of age, DNA methylation changes within paired DNA samples from the same individual reflect the impact of diverse neonatal experiences. Genes coding for critical cellular–metabolic enzymes, ion channels and receptors were more methylated in pups exposed to the adverse environment, predictive of their repression. In contrast, the adverse experience was associated with less methylation on genes involved in pathways of death and inflammation as well as cell-fate related transcription factors, indicating their potential upregulation. Thus, intra-individual methylome signatures indicate large-scale transcription-driven alterations of cellular fate, growth and function.

scholarly journals Deciphering Local Adaptation Of Native Indian Cattle (Bos Indicus) Breeds Using Landscape Genomics And In-Silico Prediction Of Deleterious SNP Effects On Protein Structure And Function

2021 ◽  
Author(s):  
Shivam Bhardwaj ◽  
Sanjeev Singh ◽  
Indrajit Ganguly ◽  
Avnish Kumar Bhatia ◽  
S. P. Dixit
Keyword(s):  
Local Adaptation ◽  
Protein Function ◽  
Bos Indicus ◽  
Climatic Conditions ◽  
Landscape Genomics ◽  
Mutant Proteins ◽  
Cattle Breeds ◽  
Native Cattle ◽  
And Function ◽  
The Impact

Abstract Present study aimed to explore genomic basis of adaptation of Indian native cattle and to predict the impact of key SNPs on amino acid changes that affect protein function. Four native cattle breeds belonging to contrasting landscape and climatic conditions were genotyped using Illumina 777 K BovineHD BeadChip: Siri & Ladakhi from cold hilly areas, and Kankrej and Hallikar from hot arid and semi-arid regions, respectively. The R.SamBada package in R was used to perform the genotype-environment association analysis. A total of 1,12,780 significant (q < 0.05), models with 30,350 unique SNPs were obtained. Significantly associated SNPs had impact on 4,435 genes and 141 pathways. Only ten SNP variants had a SIFT score of < 0.05 (deleterious), and only two of them, each lying in the genes CRYBA1 and USP18, were predicted to be deleterious with high confidence.. RaptorX predicted the tertiary structures of proteins encoded by wild and mutant variants of these genes. The quality of the models was determined using Ramachandran plots and RaptorX parameters, indicating that they are accurate. RaptorX and I-Mutant 2.0 softwares revealed significant differences among wild and mutant proteins. Identified adaptive alleles might be responsible for the local adaptation of these cattle breeds.

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