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Marlou Snelleman 2011

HOPE. Have (y)Our Protein Explained. Marlou Snelleman 2011. Overview. When and why do you use HOPE? How to use HOPE? How does HOPE work?. When and why do you use HOPE?. HOPE is useful when you are studying (point) mutations on protein level Using HOPE can save a lot of time

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Marlou Snelleman 2011

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  1. HOPE Have (y)Our Protein Explained MarlouSnelleman 2011

  2. Overview • When and why do you use HOPE? • How to use HOPE? • How does HOPE work?

  3. When and why do you use HOPE? • HOPE is useful when you are studying (point) mutations on protein level • Using HOPE can save a lot of time • Pre-select mutations that are expected to have effect • Quick information without examining multiple databases and programs • No need for complete knowledge of bioinformatics

  4. How to use HOPE? • HOPE needs the sequence as input

  5. How to use HOPE?

  6. How does HOPE work?

  7. BLAST Input • The sequence • The mutation • Object: The sequence • Tool: BLAST • Information: • Uniprot • Additional information • Domains, active sites, phosphorylation sites, contacts, cysteine bridges, variants etc. • PDB • Structural information

  8. Uniprot • Database that contains • Protein sequences • Protein information • Function • Origin • Position of active site(s) • Position of phosphorylation site(s) • Domains • Etc. • Cross-links to other databases • Etc.

  9. PDB Structure or model • 100% identity? • Use this PDB structure • Less than 100% identity? • Make a model • when the sequences are longer than 80 amino acids and the identity is higher than 25% (Sander and Schneider curve) • with the YASARA and WHAT IF Twinset

  10. Structure or modelStructural analysis • Object: Structure or model • Tool: WHAT IF • Information: Clashes, disturbed contacts, etc.

  11. PDB No structure • Object: The sequence • Tool: DAS-servers • Information: prediction of for example phosphorylation sites.

  12. HSSP Conservation scores • Object: The sequence • Tool: HSSP • Information: conservation scores Comparison of properties • Object: The wild type and the mutant amino acids • Information: comparison of the different properties of the amino acids

  13. Output

  14. One example: LRTOMT • Mutations in the LRTOMT gene cause deafness • One of these mutations: Y111L

  15. One example: LRTOMT • HOPE:

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