Titre : Multistate Computational protein Design with Backbone Ensembles: Applications in Protein Engineering and Systems Biology.
Endroit : Pavillon Roger-Gaudry, salle G-815 à 11 h
Hôte : Professeure Joelle Pelletier
La conférence sera prononcée (en anglais) par le professeur Roberto Chica, du Département de chimie de l'Université d'Ottawa.
Résumé : Computational protein design (CPD) is a useful tool for protein engineers. It has been successfully applied towards the creation of proteins with increased stability, improved binding affinity, novel enzymatic activity, and altered ligand specificity. Traditionally, CPD calculations search and rank sequences using a single fixed protein backbone template in an approach referred to as single-state design. Despite numerous successes, singlestate design is prone to false negative predictions that result from the combined use of a single fixed backbone template and a discrete set of rigid rotamers. This known artefact of single-state design leads to the incorrect rejection of sequences that could have been otherwise tolerated using slightly different rotamer and backbone geometries during calculation. This fixed backbone approximation can be addressed with multistate design, an emerging methodology in CPD that considers any number of protein conformational states as inputs to calculation. Multistate design improves the prediction of stable and functional protein
sequences by using backbone ensembles approximating conformational flexibility as input templates instead of a single fixed protein structure. In this presentation, we will show how multistate design with backbone ensembles can be successfully applied towards (1) the design of stable globular proteins with accurately predicted stability, (2) the control of protein conformational equilibrium, and (3) the discovery of substrates for an enzyme depositing posttranslational modifications.
