Dr. David C. Schriemer
Dept. of Biochemistry & Molecular Biology, University of Calgary, Calgary Canada
Structural proteomics: a bioanalytical toolkit for modeling protein systems using mass spectrometry
Integrative methods in structural biology use data from various sources to generate accurate models of large multi-protein assemblies. The approach uses available protein structures as the “building blocks” of a large assembly, and combines them with biophysical data collected on the assembly. If the data contain sufficient spatial information, molecular modeling can generate accurate models of the whole. In this way, the classical techniques used in structure determination can reach beyond their current limitations. Accurate molecular models of impressive size and complexity can be generated that lead to new biological insights, and new opportunities for drug development.
The field of integrative structure determination is still young, and it lacks sufficiently rich sources of biophysical data to constrain the model-building exercise. Mass spectrometry (MS) has enormous potential to serve as a key provider of structural restraints. Methods are emerging that provide information on protein shape, topography, orientation and dynamics, but significant analytical and informatics challenges have limited MS to smaller systems. This presentation will describe our vision for structural proteomics, and our progress towards generating a complete bioanalytical platform that supports an MS-based structural analysis of ultra-large protein systems. Our strategy involves coding protein structure into mass-readable signatures via chemical labeling. We use photolytic reagents (for interface mapping), hydrogen/deuterium exchange (for protein dynamics) and crosslinking (for structure and orientation). Using examples drawn from our research in mitotic regulation, DNA damage repair and vaccine development, I will highlight new methods for installing and measuring these structural codes that scale well to large protein systems. I will introduce a new software framework that we developed to support MS-driven structure-building activities (Mass Spec Studio, www.msstudio.ca).
Date(s) - January 17, 2017
6:00 pm - 9:00 pm
Emplacement / Location
Morris and Rosalind Goodman Agora