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Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces.

Venselaar H, Te Beek TA, Kuipers RK, Hekkelman ML, Vriend G - BMC Bioinformatics (2010)

Bottom Line: We tested HOPE by comparing its output to the results of manually performed projects.The use of 3D structures helps optimize the results in terms of reliability and details.HOPE's results are easy to understand and are presented in a way that is attractive for researchers without an extensive bioinformatics background.

View Article: PubMed Central - HTML - PubMed

Affiliation: CMBI, NCMLS, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, Netherlands. h.venselaar@cmbi.ru.nl

ABSTRACT

Background: Many newly detected point mutations are located in protein-coding regions of the human genome. Knowledge of their effects on the protein's 3D structure provides insight into the protein's mechanism, can aid the design of further experiments, and eventually can lead to the development of new medicines and diagnostic tools.

Results: In this article we describe HOPE, a fully automatic program that analyzes the structural and functional effects of point mutations. HOPE collects information from a wide range of information sources including calculations on the 3D coordinates of the protein by using WHAT IF Web services, sequence annotations from the UniProt database, and predictions by DAS services. Homology models are built with YASARA. Data is stored in a database and used in a decision scheme to identify the effects of a mutation on the protein's 3D structure and function. HOPE builds a report with text, figures, and animations that is easy to use and understandable for (bio)medical researchers.

Conclusions: We tested HOPE by comparing its output to the results of manually performed projects. In all straightforward cases HOPE performed similar to a trained bioinformatician. The use of 3D structures helps optimize the results in terms of reliability and details. HOPE's results are easy to understand and are presented in a way that is attractive for researchers without an extensive bioinformatics background.

Show MeSH
HOPE's input screen. The user can submit a sequence of interest and indicate the mutated residue with two simple mouse-clicks. In this example HOPE will analyze a leucine to proline mutation on position 25 of the plant protein Crambin.
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Figure 2: HOPE's input screen. The user can submit a sequence of interest and indicate the mutated residue with two simple mouse-clicks. In this example HOPE will analyze a leucine to proline mutation on position 25 of the plant protein Crambin.

Mentions: The intended users of HOPE are life scientists who neither routinely use protein structures nor bioinformatics in their research. Therefore, both HOPE's input and its results are designed to be intuitive and simple, and all software used will run with default settings so that the user neither needs to set parameters nor needs to read documentation. Actually, the user will not even know which software runs in the background. The interface of HOPE is a website that enables the user to submit a sequence and a mutation. The user can indicate the mutated residue and the new residue type by simple mouse-clicks. Figure 2 shows the input screen, filled with an example protein sequence and a mutation.


Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces.

Venselaar H, Te Beek TA, Kuipers RK, Hekkelman ML, Vriend G - BMC Bioinformatics (2010)

HOPE's input screen. The user can submit a sequence of interest and indicate the mutated residue with two simple mouse-clicks. In this example HOPE will analyze a leucine to proline mutation on position 25 of the plant protein Crambin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2992548&req=5

Figure 2: HOPE's input screen. The user can submit a sequence of interest and indicate the mutated residue with two simple mouse-clicks. In this example HOPE will analyze a leucine to proline mutation on position 25 of the plant protein Crambin.
Mentions: The intended users of HOPE are life scientists who neither routinely use protein structures nor bioinformatics in their research. Therefore, both HOPE's input and its results are designed to be intuitive and simple, and all software used will run with default settings so that the user neither needs to set parameters nor needs to read documentation. Actually, the user will not even know which software runs in the background. The interface of HOPE is a website that enables the user to submit a sequence and a mutation. The user can indicate the mutated residue and the new residue type by simple mouse-clicks. Figure 2 shows the input screen, filled with an example protein sequence and a mutation.

Bottom Line: We tested HOPE by comparing its output to the results of manually performed projects.The use of 3D structures helps optimize the results in terms of reliability and details.HOPE's results are easy to understand and are presented in a way that is attractive for researchers without an extensive bioinformatics background.

View Article: PubMed Central - HTML - PubMed

Affiliation: CMBI, NCMLS, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, Netherlands. h.venselaar@cmbi.ru.nl

ABSTRACT

Background: Many newly detected point mutations are located in protein-coding regions of the human genome. Knowledge of their effects on the protein's 3D structure provides insight into the protein's mechanism, can aid the design of further experiments, and eventually can lead to the development of new medicines and diagnostic tools.

Results: In this article we describe HOPE, a fully automatic program that analyzes the structural and functional effects of point mutations. HOPE collects information from a wide range of information sources including calculations on the 3D coordinates of the protein by using WHAT IF Web services, sequence annotations from the UniProt database, and predictions by DAS services. Homology models are built with YASARA. Data is stored in a database and used in a decision scheme to identify the effects of a mutation on the protein's 3D structure and function. HOPE builds a report with text, figures, and animations that is easy to use and understandable for (bio)medical researchers.

Conclusions: We tested HOPE by comparing its output to the results of manually performed projects. In all straightforward cases HOPE performed similar to a trained bioinformatician. The use of 3D structures helps optimize the results in terms of reliability and details. HOPE's results are easy to understand and are presented in a way that is attractive for researchers without an extensive bioinformatics background.

Show MeSH