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Integrative visual analysis of protein sequence mutations.

Doncheva NT, Klein K, Morris JH, Wybrow M, Domingues FS, Albrecht M - BMC Proc (2014)

Bottom Line: An important aspect of studying the relationship between protein sequence, structure and function is the molecular characterization of the effect of protein mutations.The views are linked tightly and synchronized to reduce the cognitive load of the user when switching between them.We demonstrate the effectiveness of our approach and the developed software on the data provided for the BioVis 2013 data contest.

View Article: PubMed Central - HTML - PubMed

Affiliation: Max Planck Institute for Informatics, 66123 Saarb├╝cken, Germany ; University of California, San Francisco, 94143-2240 San Francisco, USA.

ABSTRACT

Background: An important aspect of studying the relationship between protein sequence, structure and function is the molecular characterization of the effect of protein mutations. To understand the functional impact of amino acid changes, the multiple biological properties of protein residues have to be considered together.

Results: Here, we present a novel visual approach for analyzing residue mutations. It combines different biological visualizations and integrates them with molecular data derived from external resources. To show various aspects of the biological information on different scales, our approach includes one-dimensional sequence views, three-dimensional protein structure views and two-dimensional views of residue interaction networks as well as aggregated views. The views are linked tightly and synchronized to reduce the cognitive load of the user when switching between them. In particular, the protein mutations are mapped onto the views together with further functional and structural information. We also assess the impact of individual amino acid changes by the detailed analysis and visualization of the involved residue interactions. We demonstrate the effectiveness of our approach and the developed software on the data provided for the BioVis 2013 data contest.

Conclusions: Our visual approach and software greatly facilitate the integrative and interactive analysis of protein mutations based on complementary visualizations. The different data views offered to the user are enriched with information about molecular properties of amino acid residues and further biological knowledge.

No MeSH data available.


Related in: MedlinePlus

Visualization of the dimer interface with focus on the mutated residues. The combined visualization of the conservation-colored RIN of chain A of scTIM (left), the residue nodes in the interface between chain A (red) and chain B (blue) of scTIM (middle), and the ribbon representation of scTIM are in the same colors as provided by UCSF Chimera (right). Mutations located in the dimer interface (V86, T45, S71, S16, Q82, N78, L13, H103, F108) are highlighted by yellow colored nodes in the network views and by green boundaries and ball-and-stick representations in the structure view. Nodes that correspond to mutated residues are depicted as diamonds.
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Figure 7: Visualization of the dimer interface with focus on the mutated residues. The combined visualization of the conservation-colored RIN of chain A of scTIM (left), the residue nodes in the interface between chain A (red) and chain B (blue) of scTIM (middle), and the ribbon representation of scTIM are in the same colors as provided by UCSF Chimera (right). Mutations located in the dimer interface (V86, T45, S71, S16, Q82, N78, L13, H103, F108) are highlighted by yellow colored nodes in the network views and by green boundaries and ball-and-stick representations in the structure view. Nodes that correspond to mutated residues are depicted as diamonds.

Mentions: Since scTIM functions as a dimer, another important aspect is the binding interface between the two monomers. We used RINalyzer to extract the residue interactions of the interface and visualized them in a separate network view. As can be seen in Figure 7, 9 out of the 69 residues are mutated (L13, S16, T45, S71, N78, Q82, V86, H103, F108). These changes might impair the dimer formation and thus affect the function of scTIM. Residue L13 is particularly interesting as it is both conserved and in the dimer interface. A similar analysis can be performed with other functional sites. For instance, we found that none of the residues in the active or substrate binding site (N10, K12, H95, E165) are mutated. However, 24 residues possess direct non-covalent interactions with functionally important residues and thus could have a severe impact on their function if mutated. This is the case for the residues F11, L13, and C41, and this observation is further strengthened by the fact that the first two of them are conserved as described above.


Integrative visual analysis of protein sequence mutations.

Doncheva NT, Klein K, Morris JH, Wybrow M, Domingues FS, Albrecht M - BMC Proc (2014)

Visualization of the dimer interface with focus on the mutated residues. The combined visualization of the conservation-colored RIN of chain A of scTIM (left), the residue nodes in the interface between chain A (red) and chain B (blue) of scTIM (middle), and the ribbon representation of scTIM are in the same colors as provided by UCSF Chimera (right). Mutations located in the dimer interface (V86, T45, S71, S16, Q82, N78, L13, H103, F108) are highlighted by yellow colored nodes in the network views and by green boundaries and ball-and-stick representations in the structure view. Nodes that correspond to mutated residues are depicted as diamonds.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4155609&req=5

Figure 7: Visualization of the dimer interface with focus on the mutated residues. The combined visualization of the conservation-colored RIN of chain A of scTIM (left), the residue nodes in the interface between chain A (red) and chain B (blue) of scTIM (middle), and the ribbon representation of scTIM are in the same colors as provided by UCSF Chimera (right). Mutations located in the dimer interface (V86, T45, S71, S16, Q82, N78, L13, H103, F108) are highlighted by yellow colored nodes in the network views and by green boundaries and ball-and-stick representations in the structure view. Nodes that correspond to mutated residues are depicted as diamonds.
Mentions: Since scTIM functions as a dimer, another important aspect is the binding interface between the two monomers. We used RINalyzer to extract the residue interactions of the interface and visualized them in a separate network view. As can be seen in Figure 7, 9 out of the 69 residues are mutated (L13, S16, T45, S71, N78, Q82, V86, H103, F108). These changes might impair the dimer formation and thus affect the function of scTIM. Residue L13 is particularly interesting as it is both conserved and in the dimer interface. A similar analysis can be performed with other functional sites. For instance, we found that none of the residues in the active or substrate binding site (N10, K12, H95, E165) are mutated. However, 24 residues possess direct non-covalent interactions with functionally important residues and thus could have a severe impact on their function if mutated. This is the case for the residues F11, L13, and C41, and this observation is further strengthened by the fact that the first two of them are conserved as described above.

Bottom Line: An important aspect of studying the relationship between protein sequence, structure and function is the molecular characterization of the effect of protein mutations.The views are linked tightly and synchronized to reduce the cognitive load of the user when switching between them.We demonstrate the effectiveness of our approach and the developed software on the data provided for the BioVis 2013 data contest.

View Article: PubMed Central - HTML - PubMed

Affiliation: Max Planck Institute for Informatics, 66123 Saarb├╝cken, Germany ; University of California, San Francisco, 94143-2240 San Francisco, USA.

ABSTRACT

Background: An important aspect of studying the relationship between protein sequence, structure and function is the molecular characterization of the effect of protein mutations. To understand the functional impact of amino acid changes, the multiple biological properties of protein residues have to be considered together.

Results: Here, we present a novel visual approach for analyzing residue mutations. It combines different biological visualizations and integrates them with molecular data derived from external resources. To show various aspects of the biological information on different scales, our approach includes one-dimensional sequence views, three-dimensional protein structure views and two-dimensional views of residue interaction networks as well as aggregated views. The views are linked tightly and synchronized to reduce the cognitive load of the user when switching between them. In particular, the protein mutations are mapped onto the views together with further functional and structural information. We also assess the impact of individual amino acid changes by the detailed analysis and visualization of the involved residue interactions. We demonstrate the effectiveness of our approach and the developed software on the data provided for the BioVis 2013 data contest.

Conclusions: Our visual approach and software greatly facilitate the integrative and interactive analysis of protein mutations based on complementary visualizations. The different data views offered to the user are enriched with information about molecular properties of amino acid residues and further biological knowledge.

No MeSH data available.


Related in: MedlinePlus