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Protein families are groups of homologous proteins; that is, they have similarities in amino acid sequences and three-dimensional structures. Protein families usually occur because of gene duplication, where an additional copy of a gene is inserted into the genome of an organism.   Mutations that change the amino acids but still allow the protein to be properly synthesized, will lead to new protein family members.   If these new proteins contain similar amino acids in key...
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Mu-8: visualizing differences between proteins and their families.

Johnathan D Mercer1, Balaji Pandian2, Alexander Lex2

  • 1Harvard University, 33 Oxford Street, MA 02138 Cambridge, USA ; Broad Institute, 7 Cambridge Center, MA 02142 Cambridge, USA.

BMC Proceedings
|September 20, 2014
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Summary

This study introduces Mu-8, an interactive visualization tool that identifies protein dysfunction by analyzing amino acid sequence, biophysical properties, and 3D structure differences within protein families.

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Area of Science:

  • Biophysical Sciences
  • Structural Biology
  • Computational Biology

Background:

  • Understanding the amino acid sequence-function relationship is crucial but challenging.
  • Current methods for identifying functionally relevant mutations overlook biophysical properties and 3D protein structure.
  • An interactive visualization technique is needed for a holistic view of protein differences within families.

Purpose of the Study:

  • To develop an interactive visualization technique, Mu-8, for analyzing protein sequence and structure.
  • To identify regions in a protein that differ significantly from homologous proteins.
  • To aid researchers in pinpointing mutations responsible for protein dysfunction.

Main Methods:

  • Developed Mu-8, an interactive visualization technique.
  • Quantified protein differences using amino acid indices and principal components.
  • Accounted for residue conservation, proximity, and 3D structural context.

Main Results:

  • Mu-8 provides a holistic view of protein differences compared to homologous families.
  • Identified candidate regions associated with protein dysfunction in a case study.
  • Demonstrated the utility of Mu-8 in analyzing dysfunctional proteins from the 2013 BioVis contest data.

Conclusions:

  • Mu-8 effectively highlights areas of significant biochemical variation, conservation, and structural proximity.
  • The tool aids in identifying potential causes of protein malfunction.
  • Mu-8 offers a novel approach to understanding protein sequence-structure-function relationships.