Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces
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
BMC Bioinformatics 2010, 11:548 doi:10.1186/1471-2105-11-548Published: 8 November 2010
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.
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.
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.