Have (y)Our Protein Explained 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 Pre-select mutations that are expected to have effect Quick information without examining multiple databases and programs No need for complete knowledge of bioinformatics

How to use HOPE? HOPE needs the sequence as input

How to use HOPE?

Structural information Comparison of properties How does HOPE work? Input BLAST PDB Structure or model Structural analysis Structural information Output No structure DAS-servers Additional information Uniprot HSSP Conservation scores Comparison of properties

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

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

PDB Structure or model 100% identity? Less than 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

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

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

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

Output Print screen van een report

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

One example: LRTOMT HOPE: