Computational Service
Protein Degrader
Scoped After Feasibility Review
Service Overview
Degrader assessment asks a different question from inhibitor assessment. Occupancy is not the endpoint, catalytic behaviour matters, and selectivity has to be judged at the level of the degraded proteome rather than the bound target. We support that assessment computationally: analysing ternary complexes, predicting ADMET and DMPK properties for molecules well outside conventional property space, and interpreting the degradation and proteomics data that establish whether a compound does what it is supposed to.
Key Features & Advantages
Selectivity Judged Proteome-Wide
Neo-substrate and off-target degradation risk is assessed against the surface and sequence features that drive it, and global proteomics data is analysed where it exists.
DMPK Prediction Fit For Purpose
Property prediction uses models appropriate to beyond-rule-of-five chemistry, and states where a compound sits outside the applicability domain rather than returning a confident-looking number.
Degradation Data Interpreted Properly
DC50, Dmax, hook behaviour and kinetics are analysed together, since a compound with excellent DC50 and poor Dmax is a different problem from the reverse.
Structure Linked To Behaviour
Observed degradation differences across a series are related back to the ternary models, which is what turns an assay result into a design instruction.
Where This Service Is Used
1Assessing a degrader candidate before committing to in vivo studies
2Investigating why two closely related degraders behave differently
3Evaluating off-target and neo-substrate degradation risk
4Analysing global proteomics data from degrader treatment experiments
5Building the computational section of a candidate selection package
How the Work Is Performed
1Ternary complex analysis with interface characterisation and stability simulation
2Off-target and neo-substrate risk assessment from structural and sequence features
3ADMET and DMPK prediction with beyond-rule-of-five appropriate models and domain checking
4Metabolic soft-spot prediction and reactive metabolite alert screening
5Degradation data analysis: DC50, Dmax, kinetics and hook behaviour across the series
6Proteomics data analysis for selectivity, with statistical treatment appropriate to the design
What We Need From You
1Degrader structures with any measured degradation, binding and property data
2Target and ligase structures or models
3Proteomics datasets where selectivity assessment is in scope, with experimental design details
4The decision the assessment supports: candidate selection, series triage or mechanism investigation
What You Receive
1Ternary complex analysis with interface and stability assessment per compound
2Predicted ADMET and DMPK profiles with confidence and applicability domain stated
3Selectivity assessment including off-target degradation risk
4Degradation data analysis relating observed behaviour to structural differences
5Proteomics analysis with figures and statistics where such data is supplied
Questions We Are Asked Before Scoping
Can you predict DC50 or Dmax?
▸No. Both depend on cellular ubiquitination and proteasome processing that computation does not resolve. We explain observed differences structurally and predict properties, which is a narrower but genuinely useful contribution.
How do we assess selectivity properly?
▸Global proteomics after treatment is the standard approach. We help design the experiment and analyse the data, including the statistics that separate genuine off-target degradation from variability.
Is computational DMPK reliable for degraders?
▸Less so than for conventional small molecules, because most models were trained on rule-of-five chemistry. We say where a compound falls outside the applicability domain instead of quoting a number regardless.
Interpretation and Limitations
This is a computational (in silico) service. Designs and predictions prioritise hypotheses and direct experimental effort; they do not by themselves establish that an edit, construct, molecule or assay will perform as intended. Laboratory execution — editing, cloning, expression, synthesis and testing — is planned with you and carried out by your own team or a qualified partner. Deliverables are for research use only and are not intended for diagnostic or therapeutic use.
Is This the Right Service for You?
Choose this when
A candidate is approaching in vivo work and needs a computational assessment
Two close analogues behave differently and the reason is unclear
Proteomics data from degrader treatment needs proper analysis
Consider another service when
New designs rather than analysis are needed
Protein Degrader Design & Synthesis Only conventional small molecule properties are in question
Toxicity & Safety Profiling What Goes Wrong, and How We Handle It
These are the failure modes that produce confident-looking results which do not survive the next experiment. Each one is designed against rather than discovered afterwards.
Selectivity judged from a handful of western blots
Proteome-wide analysis is recommended and analysed with statistics matched to the design, since off-target degradation is the question.
Standard property models applied to degrader-sized molecules
Beyond-rule-of-five models are used and applicability-domain status is stated per compound.
DC50 and Dmax treated as one property
Potency and maximum degradation are analysed separately, because a good DC50 with poor Dmax is a different problem from the reverse.
A Worked Example
Two analogues, same binding, different degradation
The situation
A methyl group difference changed Dmax substantially while binary affinity was unchanged.
What the work involved
Ternary complexes were modelled and simulated for both, interface contacts were compared, and the degradation data was analysed against the structural difference.
What came back
The methyl group added a contact at the target–ligase interface that stabilised the complex. Six further designs exploited the same contact, and the interface was flagged as the thing to optimise.
Illustrative of the shape this work takes. Details are generalised, no client or target is identified, and scope and outcome vary with the system in question.
What Published Work Reports
The results below were published by independent groups and are cited to show what these computational approaches have achieved in the literature. They are not ICDMO project results, and outcomes vary substantially between targets, datasets and programmes. We do not promise comparable results for any particular project.
Property prediction is accurate enough to triage, not to replace measurement
Across the published literature, lipophilicity and surface-property predictions are generally reliable, while aqueous solubility models typically carry errors around one log unit and absolute human pharmacokinetic prediction remains weak. We therefore report predictions with their expected error and applicability-domain status, and recommend measurement at the point where a decision turns on the number rather than the rank order.
Method comparison literature, ongoing ↗Service Workflow
1
Scientific Consultation
We discuss the objective, the decision it supports and the material and data you already hold.
2
Feasibility Review
We check that the target, system and available information can support the approach, and say plainly where they cannot.
3
Technical Proposal
Scope, methods, deliverables, timeline and price are confirmed in writing, together with the limitations we expect to report.
4
Design and Analysis
The design work runs on documented tools and parameters, with quality checks and alternatives compared where that is informative.
5
Delivery and Follow-Up
You receive the designs, the supporting analysis and a validation plan, plus support interpreting the results once the experiments run.
Service Process
1
Online Consultation
›
2
Solution Matching
›
3
Service Contract
›
4
Project Execution
›
5
Data Delivery
Specifications & Turnaround
Note: ICDMO delivers computational (in silico) services. Results prioritise hypotheses for testing; they do not by themselves establish binding, biological activity, efficacy or safety. All deliverables are for research use only and are not intended for diagnostic or therapeutic use. Downstream experimental work is scoped separately and executed through qualified partners.
Get a Custom Quote
Our scientific team responds within 24 hours with a detailed technical proposal and pricing tailored to your project.
Contact Us Online ConsultationStandard Deliverables
✓Sequence-verified final product
✓Full QC documentation
✓Certificate of Analysis (CoA)
✓Electronic data files
✓Project completion report
Why ICDMO?
Computational CDMO Focus
Reproducible, Versioned Pipelines
Confidence & Limitations Reported
Experiment-Aware Recommendations
Response Within One Business Day