Ultrasensitive, High-Throughput nanoHDX-MS for Insights into Protein Dynamics and Interactions

Hydrogen/deuterium exchange-mass spectrometry (HDX-MS) is a powerful technique for studying protein dynamics, however its widespread application has been constrained by high sample consumption and lengthy analysis times. This webinar will introduce a novel, fully automated nano-flow HDX-MS (nHDX-MS) platform that overcomes these critical limitations, ushering in a new era of sensitivity and throughput in structural proteomics. By integrating nanoflow liquid chromatography with a fully automated sample preparation and data analysis workflow, our innovative approach achieves a remarkable >50-fold increase in sensitivity over traditional microflow methods. This technological leap enables the analysis of precious, low-abundance proteins and large complexes using only a few pmol of material per experiment, with the added benefit of same-day results.

This presentation will delve into the key innovations of our nHDX-MS platform, a technology that delivers robust and reproducible data for a wide array of applications. We will showcase its power and versatility through several case studies—from interrogating protein-ligand interactions and performing high-throughput epitope mapping to characterizing large, dynamic protein complexes. These examples will highlight the significant impact of this technology on accelerating drug discovery and advancing our fundamental understanding of protein function.

Learning Objectives:

• Learn design and operational workflow of nano-flow HDX-MS
• Discover application of HDX-MS for protein-ligand interactions and epitope mapping to characterizing large, dynamic protein complexes. 
• Learn about key innovations in HDX-MS

Presenter: Malvina Papanastasiou, Ph.D. (Group Leader, Broad Institute of MIT & Harvard)

Malvina Papanastasiou is a Group Leader and Research Scientist at the Broad Institute of MIT & Harvard, where she spearheads structural proteomics initiatives using hydrogen/deuterium exchange (HDX−MS) and cross-linking mass spectrometry (XL−MS). She has over fifteen years of experience leading interdisciplinary efforts in drug discovery, epigenetics, immunology, and cancer research. Her work focuses on understanding protein structure-function relationships, characterizing protein-ligand and protein-protein interactions. Dr. Papanastasiou contributes her expertise to multiple high-profile research consortia funded by the NIH and HHMI and serves as the Vice-Chair of the International Society of HDX-MS.

Prior to joining the Broad Institute in 2016, her career included postdoctoral research at the Center for Drug Discovery at Northeastern University and a fellowship at the Perelman School of Medicine at the University of Pennsylvania. She also worked as a research scientist at the Foundation for Research and Technology in Greece, during which time she was an EMBO visiting fellow at the University of Southern Denmark.