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Open Access Highly Accessed Methodology article

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

Hanka Venselaar1*, Tim AH te Beek2, Remko KP Kuipers34, Maarten L Hekkelman1 and Gert Vriend1

Author Affiliations

1 CMBI, NCMLS, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, Netherlands

2 NBIC, Netherlands Bioinformatics Centre, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands

3 Laboratory of Systems and Synthetic Biology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands

4 BioProdict, Dreijenplein 10, 6703 HB Wageningen, The Netherlands

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BMC Bioinformatics 2010, 11:548  doi:10.1186/1471-2105-11-548

Published: 8 November 2010

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.