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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
Detailed overview of HOPE's components. HOPE's input consists of the sequence and the mutation. The sequence is used for a BLAST search against the databases. Using the accession code (and PDB-file if available) HOPE can collect information from a series of information sources: WHAT IF calculations on the PDB-file or homology model built by YASARA, annotations in the Uniprot database, HSSP conservation scores and sequence-based predictions by DAS-servers. The information is combined in a decision scheme and a report is generated. This report is illustrated with pictures and animations and difficult keywords are linked to our own online dictionary.
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Figure 5: Detailed overview of HOPE's components. HOPE's input consists of the sequence and the mutation. The sequence is used for a BLAST search against the databases. Using the accession code (and PDB-file if available) HOPE can collect information from a series of information sources: WHAT IF calculations on the PDB-file or homology model built by YASARA, annotations in the Uniprot database, HSSP conservation scores and sequence-based predictions by DAS-servers. The information is combined in a decision scheme and a report is generated. This report is illustrated with pictures and animations and difficult keywords are linked to our own online dictionary.

Mentions: The HOPE system is schematically shown in Figure 5. The individual elements of his schema are described in the remainder of this section.


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)

Detailed overview of HOPE's components. HOPE's input consists of the sequence and the mutation. The sequence is used for a BLAST search against the databases. Using the accession code (and PDB-file if available) HOPE can collect information from a series of information sources: WHAT IF calculations on the PDB-file or homology model built by YASARA, annotations in the Uniprot database, HSSP conservation scores and sequence-based predictions by DAS-servers. The information is combined in a decision scheme and a report is generated. This report is illustrated with pictures and animations and difficult keywords are linked to our own online dictionary.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Detailed overview of HOPE's components. HOPE's input consists of the sequence and the mutation. The sequence is used for a BLAST search against the databases. Using the accession code (and PDB-file if available) HOPE can collect information from a series of information sources: WHAT IF calculations on the PDB-file or homology model built by YASARA, annotations in the Uniprot database, HSSP conservation scores and sequence-based predictions by DAS-servers. The information is combined in a decision scheme and a report is generated. This report is illustrated with pictures and animations and difficult keywords are linked to our own online dictionary.
Mentions: The HOPE system is schematically shown in Figure 5. The individual elements of his schema are described in the remainder of this section.

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