Development of a Protein Conservation Analysis Pipeline and Application to Carbonic Anhydrase IV
BARKER, HARLAN (2013)
2013
Bioinformatiikka - Bioinformatics
Biolääketieteellisen teknologian yksikkö - Institute of Biomedical Technology
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Hyväksymispäivämäärä
2013-10-11
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:uta-201310291527
https://urn.fi/URN:NBN:fi:uta-201310291527
Tiivistelmä
*Background and Aims * Conservation is a hallmark of inherent valuable function. Computational analysis of conservation of each amino acid in a protein provides targets for future computational or experimental research. Carbonic anhydrases (CA) reversibly catalyze the carbon dioxide to bicarbonate reaction. Despite the apparent simplicity of the reaction, the ?-CA protein family exists as more than 15 different isoforms in mammals and its members are present in a wide array of tissues and perform a variety of functions. The overall goal of this research is identification of all residues of functional significance in CA-IV through utilization of gene prediction, comparative genomics, and conservation analysis. The expanded goal is to make this process applicable to any protein group.
*Methods* Automated methods were created, using Python scripting, to extract orthologs for human carbonic anhydrases. Predictions were made for incomplete orthologs, and conservation analysis was performed on a codon alignment of the final set. Additional python scripts created three dimensional (3D) models of conservation values, within specific taxa or as comparisons between them.
*Results* A pipeline was created for automated gene annotation, 3D image generation, andcomparative analysis between different taxa. A total of 499 residue positions were altered in 55 carbonic anhydrase proteins from 6 isozyme types. Key amino acids have been identified in a region potentially related to CA-IV ion channel binding.
*Conclusions * Ka/Ks conservation analysis can be applied in a quick and automated manner to produce models and images from large numbers of orthologs, allowing for determination of critical amino acid residues in proteins.
*Methods* Automated methods were created, using Python scripting, to extract orthologs for human carbonic anhydrases. Predictions were made for incomplete orthologs, and conservation analysis was performed on a codon alignment of the final set. Additional python scripts created three dimensional (3D) models of conservation values, within specific taxa or as comparisons between them.
*Results* A pipeline was created for automated gene annotation, 3D image generation, andcomparative analysis between different taxa. A total of 499 residue positions were altered in 55 carbonic anhydrase proteins from 6 isozyme types. Key amino acids have been identified in a region potentially related to CA-IV ion channel binding.
*Conclusions * Ka/Ks conservation analysis can be applied in a quick and automated manner to produce models and images from large numbers of orthologs, allowing for determination of critical amino acid residues in proteins.