In the fast-moving pharmaceutical industry where new drug discovery technologies and therapeutic modalities are applied almost daily, it is expected that data science will improve the efficiency in the identification of drug targets, find good chemical scaffolds from data libraries, guide chemical synthesis and move the goalposts to select drug candidates. However, there are challenges to overcome associated with this process. A case in point is the vast number of protein-ligand interactions where the link between biochemical behavior and structural biology is not yet understood.  Although computational approaches (e.g., docking methods, molecular dynamics simulations etc.) can hypothesize the bound poses of ligands for a targeted protein, these predicted events must be validated by biophysical/structural approaches. In this context, Hydrogen/deuterium-exchange coupled to mass spectrometry (HDX-MS) is expected to continue developing as a method to study the characterization of protein dynamics following ligand binding in solution (where “ligand” could be a protein partner, a natural substrate, a peptide, or a small molecule).<br/>In this presentation we will discuss the broad applicability of HDX-MS to characterize the dynamics of a set of protein-protein interactions in solution (e.g., to examine the protein alone and in complex with its receptor) and to identify how the amide hydrogen bonding network of ligands and the protein forms are altered by binding interactions. These data will be used to probe proteins as druggable targets, validate direct binding events from molecular dynamics simulation studies and to complement structural biology information.

Insights into the role of HDX-MS in medicinal chemistry

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.