An overview of recent advances in structural bioinformatics of protein–protein interactions and a guide to their principles

Sudha, G.; Nussinov, Ruth; Srinivasan, Narayanaswamy

doi:10.1016/j.pbiomolbio.2014.07.004

Cited by 65 publications

(47 citation statements)

References 170 publications

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“…Representing interactions as networks provides a conceptual framework for understanding how mutations in proteins can affect entire cellular systems and cause disease (Wang et al., 2011, Wu et al., 2010), especially when combined with structural analyses of interacting proteins (Sudha et al., 2014, Wang et al., 2012). Here, we investigated the interaction properties and structural features of thousands of putative fusion proteins.…”

Section: Discussionmentioning

confidence: 99%

Molecular Principles of Gene Fusion Mediated Rewiring of Protein Interaction Networks in Cancer

et al. 2016

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SummaryGene fusions are common cancer-causing mutations, but the molecular principles by which fusion protein products affect interaction networks and cause disease are not well understood. Here, we perform an integrative analysis of the structural, interactomic, and regulatory properties of thousands of putative fusion proteins. We demonstrate that genes that form fusions (i.e., parent genes) tend to be highly connected hub genes, whose protein products are enriched in structured and disordered interaction-mediating features. Fusion often results in the loss of these parental features and the depletion of regulatory sites such as post-translational modifications. Fusion products disproportionately connect proteins that did not previously interact in the protein interaction network. In this manner, fusion products can escape cellular regulation and constitutively rewire protein interaction networks. We suggest that the deregulation of central, interaction-prone proteins may represent a widespread mechanism by which fusion proteins alter the topology of cellular signaling pathways and promote cancer.

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Section: Discussionmentioning

confidence: 99%

Molecular Principles of Gene Fusion Mediated Rewiring of Protein Interaction Networks in Cancer

et al. 2016

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“…Comprehensive biophysical and biochemical characterization of the binding molecules, confirmation of their target recognition abilities, and ideally the detailed atomic resolution of the binding interface is required [214] Molecules with moderate affinity to the target or with unfavorable characteristics (low solubility, aggregation, toxicity, etc) are subjected to several rounds of affinity maturation under conditions of increased stringency with special emphasis on selecting high stability compounds. This is usually carried out through random mutagenesis of variable regions (sometimes involving the scaffold), or by applying more focused approaches guided by rational computer aided design based on structural data and the results of comprehensive mutational scanning, generating heatmaps of antigen-binding enrichment ratios [166, 214-220]. Quite often maturation rounds are performed in different library screening settings and display methods used during primary selection rounds can be complemented by Y2H for affinity evolution.…”

Section: Selection Techniquesmentioning

confidence: 99%

Peptide Aptamers: Development and Applications

Reverdatto¹,

Burz²,

Shekhtman

2015

CTMC

151

104

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Peptide aptamers are small combinatorial proteins that are selected to bind to specific sites on their target molecules. Peptide aptamers consist of short, 5-20 amino acid residues long sequences, typically embedded as a loop within a stable protein scaffold. Various peptide aptamer scaffolds and in vitro and in vivo selection techniques are reviewed with emphasis on specific biomedical, bioimaging, and bioanalytical applications.

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“…In particular, what has significantly increased the achievements of molecular biology is bioinformatics, since this tool has enabled to read, interpret, and analyze huge amounts of data such as those generated from a high-throughput sequencing process in less time and with more accuracy. Some of the achievements of both molecular biology and bioinformatics include functional genomics, where is possible to study genes, proteins, and protein function, gene and protein expression in a cell under given conditions, 3D model generation in order to predict protein structure and function or pharmaceutical targets [15, 16], and presentation of molecular pathways in order to understand gene-disease interactions [17], among others.…”

Section: Introductionmentioning

confidence: 99%

Colombia, an unknown genetic diversity in the era of Big Data

P¹,

Muñoz²,

Mosquera-Rendón³

et al. 2018

BMC Genomics

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BackgroundLatin America harbors some of the most biodiverse countries in the world, including Colombia. Despite the increasing use of cutting-edge technologies in genomics and bioinformatics in several biological science fields around the world, the region has fallen behind in the inclusion of these approaches in biodiversity studies. In this study, we used data mining methods to search in four main public databases of genetic sequences such as: NCBI Nucleotide and BioProject, Pathosystems Resource Integration Center, and Barcode of Life Data Systems databases. We aimed to determine how much of the Colombian biodiversity is contained in genetic data stored in these public databases and how much of this information has been generated by national institutions. Additionally, we compared this data for Colombia with other countries of high biodiversity in Latin America, such as Brazil, Argentina, Costa Rica, Mexico, and Peru.ResultsIn Nucleotide, we found that 66.84% of total records for Colombia have been published at the national level, and this data represents less than 5% of the total number of species reported for the country. In BioProject, 70.46% of records were generated by national institutions and the great majority of them is represented by microorganisms. In BOLD Systems, 26% of records have been submitted by national institutions, representing 258 species for Colombia. This number of species reported for Colombia span approximately 0.46% of the total biodiversity reported for the country (56,343 species). Finally, in PATRIC database, 13.25% of the reported sequences were contributed by national institutions. Colombia has a better biodiversity representation in public databases in comparison to other Latin American countries, like Costa Rica and Peru. Mexico and Argentina have the highest representation of species at the national level, despite Brazil and Colombia, which actually hold the first and second places in biodiversity worldwide.ConclusionsOur findings show gaps in the representation of the Colombian biodiversity at the molecular and genetic levels in widely consulted public databases. National funding for high-throughput molecular research, NGS technologies costs, and access to genetic resources are limiting factors. This fact should be taken as an opportunity to foster the development of collaborative projects between research groups in the Latin American region to study the vast biodiversity of these countries using ‘omics’ technologies.

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An overview of recent advances in structural bioinformatics of protein–protein interactions and a guide to their principles

Cited by 65 publications

References 170 publications

Molecular Principles of Gene Fusion Mediated Rewiring of Protein Interaction Networks in Cancer

Molecular Principles of Gene Fusion Mediated Rewiring of Protein Interaction Networks in Cancer

Peptide Aptamers: Development and Applications

Colombia, an unknown genetic diversity in the era of Big Data

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