It’s important to lay strong foundations for successful drug discovery at this first stage of the process. Our integrated target identification and validation platform combines AI with expert insights, and rigorous lab validation to guide targets through robust evaluation, ready for hit discovery.
Validated, high-quality hits, delivered through integrated technologies and expert collaboration, give you a confident starting point for faster drug discovery.
Turning promising leads into clinical candidates with speed, precision, and the scientific expertise to generate high-quality data and deliver real patient impact.
Discover precise insights into brain neurochemistry with Sygnature Discovery's in vivo microdialysis and cOFM services. With over 20 years of expertise, we design bespoke studies that reveal how compounds modulate neurotransmitter systems in health and disease. Using UHPLC/HPLC with electrochemical detection or mass spectrometry, we deliver robust PK/PD data to support confident CNS decision making.
Delivering integrated, modality-agnostic drug discovery to tackle complex biology, accelerate development, and advance innovative therapies with confidence.
Advancing next-generation ADCs through payload-focused design, integrated expertise, and collaborative innovation to deliver safer, more selective therapies.
Driving biologics innovation through integrated design, structural biology, and multidisciplinary expertise to accelerate next-generation therapies from concept to clinic.
Combining deep therapeutic expertise with translational insight to design strategies, reduce risk, and accelerate discovery programs toward clinical success.
Accelerating oncology drug discovery through integrated expertise, innovative modalities, and translational insight to deliver candidates with real clinical impact.
Driving immunology and inflammation drug discovery through tailored assays, translational models, and integrated expertise for faster clinical success.
Advancing CNS drug discovery through integrated models, translational biomarkers, and multidisciplinary expertise to overcome complexity and accelerate therapeutic innovation.
Designing and advancing differentiated small-molecule therapies for obesity and diabetes through integrated expertise, mechanistic insight, and translational strategies.
Inobrodib, an exciting, first-in-class oral anti-cancer drug in clinical development by CellCentric, was collaboratively designed, synthesised and supported on its pre-clinical journey by an integrated project team at Sygnature Discovery. Inobrodib is now showing promising results in Phase I and II trials for multiple myeloma and other cancer types.
It’s important to lay strong foundations for successful drug discovery at this first stage of the process. Our integrated target identification and validation platform combines AI with expert insights, and rigorous lab validation to guide targets through robust evaluation, ready for hit discovery.
Validated, high-quality hits, delivered through integrated technologies and expert collaboration, give you a confident starting point for faster drug discovery.
Turning promising leads into clinical candidates with speed, precision, and the scientific expertise to generate high-quality data and deliver real patient impact.
Delivering integrated, modality-agnostic drug discovery to tackle complex biology, accelerate development, and advance innovative therapies with confidence.
Advancing next-generation ADCs through payload-focused design, integrated expertise, and collaborative innovation to deliver safer, more selective therapies.
Driving biologics innovation through integrated design, structural biology, and multidisciplinary expertise to accelerate next-generation therapies from concept to clinic.
Combining deep therapeutic expertise with translational insight to design strategies, reduce risk, and accelerate discovery programs toward clinical success.
Accelerating oncology drug discovery through integrated expertise, innovative modalities, and translational insight to deliver candidates with real clinical impact.
Driving immunology and inflammation drug discovery through tailored assays, translational models, and integrated expertise for faster clinical success.
Advancing CNS drug discovery through integrated models, translational biomarkers, and multidisciplinary expertise to overcome complexity and accelerate therapeutic innovation.
Designing and advancing differentiated small-molecule therapies for obesity and diabetes through integrated expertise, mechanistic insight, and translational strategies.
Inobrodib, an exciting, first-in-class oral anti-cancer drug in clinical development by CellCentric, was collaboratively designed, synthesised and supported on its pre-clinical journey by an integrated project team at Sygnature Discovery. Inobrodib is now showing promising results in Phase I and II trials for multiple myeloma and other cancer types.
QM-Driven drug design with Fragment Molecular Orbital (FMO)
FMO-SP is Sygnature’s integrated drug discovery platform, translating Fragment Molecular Orbital (FMO) theory into practical computational tools, workflows, and decision support for medicinal chemistry. It reveals residue-specific interactions often missed by classical methods, enabling more confident design, earlier pattern recognition, and clearer progression of complex targets. Delivered via an in-house platform with dedicated high-performance computing, FMO-SP provides rapid access to insights when needed. By uncovering the forces driving binding, selectivity, and SAR, it turns quantum-level data into clear, actionable guidance for medicinal chemistry programs.
Classical force fields can overlook the subtle forces that shape binding, selectivity, and molecular behavior.
These include electrostatics, charge transfer, and dispersion interactions. They become especially important in complex systems such as PPIs, ADCs, PROTACs, and RNA binders. The Fragment Molecular Orbital (FMO) method provides residue‑level insight into these effects. It explains why compounds behave a certain way and how small changes at the atomic level influence the overall binding profile.
Sygnature’s FMO‑SP builds on this capability. It combines high throughput FMO calculations with automated structure setup, streamlined fragmentation, and optimization tools. This allows project teams to explore binding energetics quickly and consistently across hit series or design hypotheses. Complex quantum information is converted into intuitive visual outputs, including heatmaps, 3D interaction maps, and electrostatic complementarity surfaces. These give medicinal chemists and computational scientists a clearer picture of the forces shaping activity.
Key Strengths
Residue‑level interaction insight
FMO‑SP quantifies residue‑specific interaction energies in kcal per mol. This helps teams see exactly which residues stabilize binding and where small structural changes can shift activity.
Clear decomposition of binding forces
Interactions are broken down into electrostatic, hydrophobic, and mixed components. This gives medicinal chemists a deeper understanding of what drives potency, selectivity, or unexpected SAR trends.
Intuitive visual outputs for rapid interpretation
Heatmaps, 3D interaction maps, and column plots turn complex quantum information into visuals that are easy to understand. These help teams spot hotspots, liabilities, and design opportunities faster.
Dynamic persistence analysis through NES or MD
When paired with NES or molecular dynamics, FMO‑SP shows which interactions remain stable and which fade as the ligand moves. This provides a more realistic view of binding behavior inside the protein environment.
Electrostatic complementarity for early safety insight
Electrostatic complementarity calculations help identify where polarity mismatches may correlate with hERG liability. This supports safer design choices earlier in hit‑to‑lead and lead optimization.
High throughput quantum workflows at scale
FMO‑SP uses GAMESS, DFTB‑PA, MP2 methods, MOE, PyMOL, KNIME, and Python pipelines to automate setup and analysis. This allows high throughput quantum mechanics to be used routinely, supporting PROTACs, molecular glues, RNA binders, and other emerging modalities.
Why Choose Sygnature for FMO-SP
The FMO‑Sygnature Platform has been applied prospectively across a broad range of target classes. It has been used to explain SAR and potency trends in GLP‑1R agonists such as Danuglipron. It has helped identify binding drivers in GPCR–peptide systems including GLP‑1R and Semaglutide. It has provided clarity on the electrostatic contributions to hERG liability in compounds like Pimozide. It has mapped cooperativity within PROTAC systems such as MZ1 and quantified ternary stabilization in molecular glue complexes including CRBN, CC‑885, and GSPT1.
These results reflect the strength of our multidisciplinary teams. Our computational chemists, medicinal chemists, and structural biologists work together to translate quantum findings into practical design recommendations. Their combined expertise accelerates DMTA cycles, reduces synthesis burden, and improves the success rate of hit‑to‑lead and lead optimization work. The mechanistic clarity generated through FMO‑SP supports regulatory documentation and IP strategies. We also remain closely aligned with the FMODD consortium, which helps ensure our methodologies reflect current best practice.
Figure 2. Examples of FMO‑SP applied across target classes. A collection of panels will show protein–ligand energetics, GPCR complementarity patterns, PPI interface hotspots, PROTAC ternary cooperativity, hERG electrostatic complementarity, and nucleic acid interaction profiles.
Leading generative artificial intelligence (GenAI) algorithms for de novo design are being used routinely within our medicinal chemistry programmes to enable rapid idea generation to address project objectives. We have successfully deployed Makya, a leading software platform for de novo molecular design from Iktos onto projects to address our client’s needs. These tools use advanced deep learning models to explore vast chemical spaces for new structures that meet multiple design criteria, such as…
Sygnature Accelerates Customers’ Drug Discovery Timelines with Improved Hit Identification, Lead Optimisation Capabilities Sygnature has…
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FAQs
We support protein–ligand systems, protein–protein interactions, GPCRs, nucleic acids, and ternary complexes such as PROTACs and molecular glue degraders.
Small molecules, peptides, biologics, PPIs, ADCs, PROTACs, molecular glues, and RNA or DNA modulators.
We run end‑to‑end workflows from input to analysis, including NES/MD integration, ESC analysis, and AI‑ready outputs. Visualizations and data files are fully automated for efficiency and clarity.
Structured CSV files containing PIE and PIEDA data, visual outputs such as heatmaps and interaction plots, 3D interaction maps, and design recommendations tailored to your program.
Related Solutions
We bring together a dynamic blend of new talent and experienced pharmaceutical industry experts from a round the world, delivering excellence across every stage of discovery.
Our Computer Aided Drug Design (CADD) capabilities combine deep scientific expertise with advanced AI, machine learning, and informatics infrastructure to support smarter, faster decision-making across the drug discovery pipeline.
Identifying key interactions isn’t always straightforward. Static models can miss critical dynamics that influence binding and stability. MD simulations allow us to observe targets in motion, uncover hidden interactions, and improve molecular design strategies.
Leveraging the properties of known active molecules to rapidly generate and optimize new compounds through ligand-driven insights, AI-powered tools, and collaborative expertise to uncover new chemical space and accelerate discovery.
