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Related Concept Videos

Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Conservation of Protein Domains02:26

Conservation of Protein Domains

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Multi-species Conserved Sequences02:51

Multi-species Conserved Sequences

Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale  studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...

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Related Experiment Video

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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
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Published on: July 14, 2015

Masking residues using context-specific evolutionary conservation significantly improves short linear motif

Norman E Davey1, Denis C Shields, Richard J Edwards

  • 1UCD Complex and Adaptive Systems Laboratory, UCD Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin, Dublin 4, Ireland.

Bioinformatics (Oxford, England)
|January 13, 2009
PubMed
Summary

We developed a new computational method to improve the discovery of short linear motifs (SLiMs) by using evolutionary information. This approach significantly enhances the identification of functional SLiMs in protein interaction datasets.

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Using SCOPE to Identify Potential Regulatory Motifs in Coregulated Genes
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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
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Using SCOPE to Identify Potential Regulatory Motifs in Coregulated Genes
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Using SCOPE to Identify Potential Regulatory Motifs in Coregulated Genes

Published on: May 31, 2011

Area of Science:

  • * Computational biology
  • * Bioinformatics
  • * Molecular biology

Background:

  • * Short linear motifs (SLiMs) are crucial for protein-protein interactions.
  • * The short and degenerate nature of SLiMs poses challenges for computational identification.
  • * Evolutionary conservation patterns can aid in SLiM discovery.

Purpose of the Study:

  • * To enhance the computational discovery of short linear motifs (SLiMs).
  • * To integrate evolutionary information into existing SLiM discovery methods.
  • * To improve the accuracy and efficiency of identifying functional SLiMs.

Main Methods:

  • * Developed a novel method to assess the evolutionary signal of residues within sequence and structural contexts.
  • * Implemented a masking strategy for under-conserved residues before SLiM discovery.
  • * Integrated this approach into the SLiMFinder statistical model.

Main Results:

  • * The new method demonstrates robustness across different conservation scores and neighborhood sizes.
  • * Significantly improved the recovery of known functional motifs from benchmarking data.
  • * Increased the identification rate of validated SLiMs from 20% to 60% in human interaction datasets.
  • * Maintained high stringency for reliable biological data analysis.

Conclusions:

  • * The developed method substantially improves the computational discovery of SLiMs.
  • * This approach offers general benefits for protein function prediction and computational annotation.
  • * The findings highlight the utility of evolutionary information in motif discovery.