Protein Analysis Group
In the Protein Analysis Group, we specialize in-depth and comprehensive analysis of proteins of pharmaceutical interest by mass spectrometry (MS). This includes analysis of the structure (primary and higher-order) and interactions of proteins, quantity of proteins in complex samples in addition to development of new MS-based analytical workflows. We aim to provide the much-needed detailed information on protein structure, purity and quantity to guide the development of new and improved drugs.
The internationally-recognized expertise and primary focus of the group is the study of protein conformation, dynamics and interactions by measuring the hydrogen/deuterium exchange of proteins by mass spectrometry (HDX-MS).
HDX-MS is a uniquely sensitive and useful technique for analyzing the solution-phase conformation and molecular interactions of protein systems that are of key pharmaceutical importance but are difficult to study by other traditional methods.
“Such protein systems include e.g. unstable or dynamic proteins, large and complex biopharmaceuticals, elusive protein-ligand/drugs interactions or membrane-embedded proteins and most our projects use HDX-MS to provide new exciting insights into such challenging yet pharmaceutically and biologically very important protein states” says Professor and Group Leader Kasper D. Rand.
The group holds state-of-the-art infrastructure for HDX-MS as well as qualitative and quantitative protein analysis by UPLC-MS and CE-MS. Our motto is that “all good science is collaborative science”. We have multiple academic and industrial collaborators within protein science and in particular have long-standing experience with successfully working at the interface between industrial and academic research. Please see publications of Kasper Rand (below) for recent and past projects.
HDX-MS with a UV laser!
In collaboration with the group of Prof. Perdita Barran at the University of Manchester and Jeff Brown at Waters Corporation, we demonstrate that MS/MS by UVPD at 213 nm can accurately measure deuterium levels in proteins at single residue resolution in HDX-MS experiments.
In collaboration with the group of Prof. Andreas Ladurner (LMU Munich), we use HDX-MS and mutagenesis to provide molecular insights into the interactions and allosteric regulation of the chromatin remodeler oncogene ALC1 and propose how it can be targeted for cancer treatment.
Membrane transport proteins
In collaboration with the group of Prof. Claus Løland (UCPH) we use HDX-MS to reveal how the conformation of a membrane transporter (LeuT) responds to ion and substrate binding. Interestingly, our data allow us to propose a refined alternating access model for substrate transport that relies on the slow partial unwinding of several transmembrane helices. The work highlights how HDX-MS can detect the slow correlated protein fluctuations that can be very important for the function of some proteins, including membrane transporters.
Staff at Protein Analysis Group
Group Leader: Kasper Dyrberg Rand