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Mu-8: visualizing differences between proteins and their families.

Mercer JD, Pandian B, Lex A, Bonneel N, Pfister H - BMC Proc (2014)

Bottom Line: A complete understanding of the relationship between the amino acid sequence and resulting protein function remains an open problem in the biophysical sciences.However, these methods do not account for the biophysical properties and the 3D structure of the protein.Mu-8 helps to identify areas of the protein that exhibit: (1) significantly different bio-chemical characteristics, (2) relative conservation in the family, and (3) proximity to other regions that have suspect behavior in the folded protein.

View Article: PubMed Central - HTML - PubMed

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

ABSTRACT

Background: A complete understanding of the relationship between the amino acid sequence and resulting protein function remains an open problem in the biophysical sciences. Current approaches often rely on diagnosing functionally relevant mutations by determining whether an amino acid frequently occurs at a specific position within the protein family. However, these methods do not account for the biophysical properties and the 3D structure of the protein. We have developed an interactive visualization technique, Mu-8, that provides researchers with a holistic view of the differences of a selected protein with respect to a family of homologous proteins. Mu-8 helps to identify areas of the protein that exhibit: (1) significantly different bio-chemical characteristics, (2) relative conservation in the family, and (3) proximity to other regions that have suspect behavior in the folded protein.

Methods: Our approach quantifies and communicates the difference between a reference protein and its family based on amino acid indices or principal components of amino acid index classes, while accounting for conservation, proximity amongst residues, and overall 3D structure.

Results: We demonstrate Mu-8 in a case study with data provided by the 2013 BioVis contest. When comparing the sequence of a dysfunctional protein to its functional family, Mu-8 reveals several candidate regions that may cause function to break down.

No MeSH data available.


The annotated Mu-8 interface showing how characteristics of a defective protein compare to its functional family.
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Figure 1: The annotated Mu-8 interface showing how characteristics of a defective protein compare to its functional family.

Mentions: We demonstrate the value of Mu-8 on the dataset published by the BioVis Data Contest, where we identify several regions of interest. Most notable are the residues at positions 150-156, which mutated from "VLEEVKD" to "LAGLGDE", shown in the focus region in Figure 1. These residues are significantly different from the family across many biophysical properties, are located in relatively conserved regions, and are close to other regions with similar anomalies in the folded protein. This region is also close to the protein's active site as lysine 12, histidine 95, and glutamic acid 165 are directly involved in the metabolic process [3]. It stands to reason that the mutated region 150-156 may have contorted the location and orientation of the active site, thus rendering the protein dysfunctional.


Mu-8: visualizing differences between proteins and their families.

Mercer JD, Pandian B, Lex A, Bonneel N, Pfister H - BMC Proc (2014)

The annotated Mu-8 interface showing how characteristics of a defective protein compare to its functional family.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4155612&req=5

Figure 1: The annotated Mu-8 interface showing how characteristics of a defective protein compare to its functional family.
Mentions: We demonstrate the value of Mu-8 on the dataset published by the BioVis Data Contest, where we identify several regions of interest. Most notable are the residues at positions 150-156, which mutated from "VLEEVKD" to "LAGLGDE", shown in the focus region in Figure 1. These residues are significantly different from the family across many biophysical properties, are located in relatively conserved regions, and are close to other regions with similar anomalies in the folded protein. This region is also close to the protein's active site as lysine 12, histidine 95, and glutamic acid 165 are directly involved in the metabolic process [3]. It stands to reason that the mutated region 150-156 may have contorted the location and orientation of the active site, thus rendering the protein dysfunctional.

Bottom Line: A complete understanding of the relationship between the amino acid sequence and resulting protein function remains an open problem in the biophysical sciences.However, these methods do not account for the biophysical properties and the 3D structure of the protein.Mu-8 helps to identify areas of the protein that exhibit: (1) significantly different bio-chemical characteristics, (2) relative conservation in the family, and (3) proximity to other regions that have suspect behavior in the folded protein.

View Article: PubMed Central - HTML - PubMed

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

ABSTRACT

Background: A complete understanding of the relationship between the amino acid sequence and resulting protein function remains an open problem in the biophysical sciences. Current approaches often rely on diagnosing functionally relevant mutations by determining whether an amino acid frequently occurs at a specific position within the protein family. However, these methods do not account for the biophysical properties and the 3D structure of the protein. We have developed an interactive visualization technique, Mu-8, that provides researchers with a holistic view of the differences of a selected protein with respect to a family of homologous proteins. Mu-8 helps to identify areas of the protein that exhibit: (1) significantly different bio-chemical characteristics, (2) relative conservation in the family, and (3) proximity to other regions that have suspect behavior in the folded protein.

Methods: Our approach quantifies and communicates the difference between a reference protein and its family based on amino acid indices or principal components of amino acid index classes, while accounting for conservation, proximity amongst residues, and overall 3D structure.

Results: We demonstrate Mu-8 in a case study with data provided by the 2013 BioVis contest. When comparing the sequence of a dysfunctional protein to its functional family, Mu-8 reveals several candidate regions that may cause function to break down.

No MeSH data available.