Ready To Start your Project?
Your discovery projects deserve to receive the best possible support – talk to the experts!
Contact UsWe offer medicinal chemistry services including CADD.
We support our client in the drug discovery process from hit identification and beyond:
- target druggability analysis
- library analysis and filtering
- virtual screening
- hit clustering & hit evaluation
- structure based drug discovery
- hit expansion
- Hit-to-Lead optimization (H2L)
- Lead Optimization (LO)
- Candidate selection
Compound Optimization Process
In the Hit-Identification phase, we search for Quality Hits. We perform Hit Expansion and SAR-exploration as essential activities to study the optimization potential of the hits. Only Quality Hits undergo further optimization in a Hit-to-Lead (H2L) optimization.
In the Hit-to-Lead (H2L) phase we optimize potency, cellular activity and other parameters that allow testing of the best compound in an in vivo proof of concept (POC) experiment.
In Lead Optimization (LO) compounds are further optimized for the desired efficacy and safety profile to identify a Candidate that is suited for further development.
Criteria for Quality Hits
We support our screening technologies with tailored workflows and specific activities to identify the most valuable hits. We have defined criteria for Quality Hits which can then be further optimized in a Hit-to-Lead (H2L) phase.
All compound optimizations are performed with the Design-Make-Test Cycle. New compounds are designed based on available data and a working hypothesis. Compounds are then synthesized and tested for their properties and activities. Finally compounds are optimized into advanced hits, quality hits, leads and candidates.
Computer Aided Drug Design (CADD)
We offer CADD (computer aided drug design) services to support drug discovery projects with:
- Computational analysis of protein dynamics
- Druggability assessment of protein targets
- Filtering of libraries and hit sets
- Prediction of physicochemical properties
- Hit clustering, hit evaluation and hit expansion
- Prediction of compound binding mode and affinity
- Structure-based virtual screening
- Pharmacophore modeling
Target Assessment
Target Assessment is essential to evaluate whether protein binding sites are suited for binding to small molecules, to fragments, covalent inhibitors or molecules beyond Rule of 5 (bRo5) that can act as disruptors of protein-protein interaction (PPIs) or as protein degraders.
Modelling is performed using experimental structures or AlphaFold2 predicted models. Dynamics of protein structure are studied by running MD Simulations and subsequent conformational analysis.
We have access to various validated tools to detect binding sites. Potential binding sites are evaluated using a Druggability Score as indicator whether sites are suited for fragments, small or large molecules.
A specific project strategy and a selected screening approach can then be devised accordingly.
- Crystal Structure-based Modeling or AlphaFold Model-based Modeling
- Molecular Dynamics (MD) Simulation
- Binding Site Detection
- Target Druggablility Prediction
Structure-based Drug Design
CADD plays an important role in our compound design process. All new design ideas go through a modelling process before they are selected for synthesis:
New compound ideas are generated as single compounds as well as larger compound series with our Computational Enumeration workflow. Molecular Docking is used to predict the potential binding poses and binding scores. After an initial scoring-based ranking, Visual Inspection is performed to analyze the plausibility of predicted binding poses. For the most attractive poses regarding protein-ligand interactions and compound strain Relative Binding Free Energy is calculated to predict the binding affinity using reference compounds for which experimental structural data and affinity data is available. For selected compound poses Molecular Dynamics Simulation is performed to study the pose stability and the protein-ligand interactions.
- Enumeration of design ideas
- Molecular Docking
- Prediction of Relative Binding Free Energy
- Molecular Dynamics Simulation
- Compound Pose Stability Analysis
Compound pose stability by ligand-residue distance plot after MD