Professor Michael Sternberg, Centre for Integrative Systems Biology and Bioinformatics, Imperial College London
Wednesday 28th January, 4.00 p.m., Stacey Lecture Theatre 1
This talk will describe computational tools we have developed for protein modelling.
Phyre2, primarily developed by Lawrence Kelley, is a widely used web server which takes a protein sequence and predicts a 3D structures based on coordinates of an homologous protein. Phyre2 includes the option PhyreAlarm which automatically notifies you if there is a new structure which yields a better model.
When in our group Mark Wass, developed tools to predict protein function from sequence (CombFun) and potential ligand binding sites (3dLigandSite).
Recently we have studied disease causing variants in protein. We showed that the interface between proteins is enriched in disease causing variants compared to the surface regions (Alessia David et al). We also identified that certain Pfam domains are more susceptible to disease than others, in part due to being hub proteins in the interactome. These concepts led to the development by Chris Yates of a web based algorithm SuSPect to predict the phenotypic effect of missense variants. SuSPect is integrated into Phyre2. SuSPect combined with interactome data yields a powerful approach to prioritise genes with missence mutations that are associated with a particular disease.