Popowicz Lab

Structure-Based Drug Discovery Group

The Structure-Based Drug Discovery (SBDD) Group is dedicated to the discovery and optimization of novel therapeutics through the integration of structural biology, biophysics, medicinal chemistry, and computational modeling. Our research focuses on understanding molecular interactions at atomic resolution to design and develop compounds with defined mechanisms of action, tailored pharmacological profiles, and therapeutic relevance. We have a strong specialization in protein–protein interaction (PPI) inhibitors and a strategic focus on rare and neglected diseases.

Experimental Drug Discovery Capabilities

Our laboratory is equipped with a comprehensive suite of biophysical and structural tools for target validation, hit identification, and lead optimization:

• NMR Spectroscopy: Used for fragment-based screening, hit validation, and detailed characterization of ligand binding via both ligand- and protein-observed experiments.

• X-ray Crystallography: High-resolution structure determination of protein–ligand complexes to guide rational design.

• Surface Plasmon Resonance (SPR) and Isothermal Titration Calorimetry (ITC): Quantitative analysis of binding affinities, kinetics, and thermodynamic profiles.

• Fluorescence-based assays: Employed for high-throughput screening, competition assays, and mechanistic studies.

• Thermal shift assays (DSF) and other biophysical platforms: Used for initial hit confirmation and selectivity profiling.

Computational Chemistry & AI-Assisted Design

We apply an extensive computational toolbox to support and accelerate all stages of the drug discovery pipeline:

• Classical and AI-based molecular docking to prioritize chemical matter based on predicted binding poses and interactions.

• Molecular Dynamics (MD) simulations for exploring protein flexibility, ligand stability, and binding mode validation.

• Free energy calculations and quantum chemistry methods for high-precision binding energy estimation and reactivity analysis.

• Cheminformatics and generative models to guide scaffold hopping, hit expansion, and ligand optimization.

This seamless integration of in silico and in vitro data enables rapid hypothesis testing and data-driven design of next-generation bioactive compounds.

Medicinal Chemistry and Chemical Biology

Our in-house medicinal chemistry lab provides the synthetic capacity to rapidly iterate on fragment and hit compounds. We design, synthesize, and characterize a wide range of molecules, including:

• Potent small-molecule inhibitors and modulators

• Fragment expansions and lead series

• PROTACs (proteolysis-targeting chimeras) and bifunctional degraders

• Covalent inhibitors and tool compounds for chemical biology

All synthetic efforts are tightly coupled with biophysical testing and structure-based optimization, forming a closed loop of design, synthesis, and evaluation.

Therapeutic Focus and Disease Areas

While our technology platform is broadly applicable, we maintain a distinct focus on challenging targets and diseases of unmet medical need. These include:

• Protein–protein interactions that are typically considered “undruggable”

• Rare genetic disorders and neglected tropical diseases

• Targets involved in host–pathogen interactions and immune regulation

• Mechanistically novel compounds with differentiated target profiles

This focus allows us to contribute meaningfully to therapeutic areas that are often underfunded or overlooked by mainstream industry pipelines.

Collaborations and Funding

Our group drives multiple drug discovery projects internally and serves as a strategic partner within the Helmholtz Association and beyond. We collaborate with academic groups, biotech companies, and pharma partners on joint research programs, target validation efforts, and translational initiatives.

The majority of our projects are funded through competitive national and international grants, including large-scale collaborative networks, disease-focused consortia, and innovation-focused programs. Our team has a proven record of delivering high-impact publications, securing intellectual property, and advancing compounds toward preclinical development.