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Chapter 4: Protein interactions and disease.

PLoS computational biology | 2012

Proteins do not function in isolation; it is their interactions with one another and also with other molecules (e.g. DNA, RNA) that mediate metabolic and signaling pathways, cellular processes, and organismal systems. Due to their central role in biological function, protein interactions also control the mechanisms leading to healthy and diseased states in organisms. Diseases are often caused by mutations affecting the binding interface or leading to biochemically dysfunctional allosteric changes in proteins. Therefore, protein interaction networks can elucidate the molecular basis of disease, which in turn can inform methods for prevention, diagnosis, and treatment. In this chapter, we will describe the computational approaches to predict and map networks of protein interactions and briefly review the experimental methods to detect protein interactions. We will describe the application of protein interaction networks as a translational approach to the study of human disease and evaluate the challenges faced by these approaches.

Pubmed ID: 23300410 RIS Download

Research resources used in this publication

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: K22 CA143148
  • Agency: NCI NIH HHS, United States
    Id: 1K22CA143148
  • Agency: NLM NIH HHS, United States
    Id: R01LM009722
  • Agency: NLM NIH HHS, United States
    Id: R01 LM009722
  • Agency: Intramural NIH HHS, United States

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This is a list of tools and resources that we have found mentioned in this publication.


Cytoscape (tool)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

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Small Molecule Pathway Database (tool)

RRID:SCR_004844

An interactive, visual database containing more than 350 small molecule pathways found in humans. More than 2/3 of these pathways (>280) are not found in any other pathway database. SMPDB is designed specifically to support pathway elucidation and pathway discovery in metabolomics, transcriptomics, proteomics and systems biology. It is able to do so, in part, by providing exquisitely detailed, fully searchable, hyperlinked diagrams of human metabolic pathways, metabolic disease pathways, metabolite signaling pathways and drug-action pathways. All SMPDB pathways include information on the relevant organs, subcellular compartments, protein cofactors, protein locations, metabolite locations, chemical structures and protein quaternary structures. Each small molecule is hyperlinked to detailed descriptions contained in the HMDB or DrugBank and each protein or enzyme complex is hyperlinked to UniProt. All SMPDB pathways are accompanied with detailed descriptions and references, providing an overview of the pathway, condition or processes depicted in each diagram. The database is easily browsed and supports full text, sequence and chemical structure searching. Users may query SMPDB with lists of metabolite names, drug names, genes / protein names, SwissProt IDs, GenBank IDs, Affymetrix IDs or Agilent microarray IDs. These queries will produce lists of matching pathways and highlight the matching molecules on each of the pathway diagrams. Gene, metabolite and protein concentration data can also be visualized through SMPDB''s mapping interface. All of SMPDB''s images, image maps, descriptions and tables are downloadable.

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