Protein Design & Engineering (AI)

De Novo Protein Design

Design of entirely new proteins with defined 3D fold, binding function, or catalytic activity. Hallucination, inpainting, and motif-scaffolding approaches.

Ref K1Computational ServiceConfidence ReportedScoped After Feasibility Review

Overview

De novo design builds proteins that have no natural counterpart: a backbone is generated to satisfy a geometric or functional requirement, a sequence is designed to fold into it, and the design is then filtered computationally before anything is expressed. The approach now produces binders, scaffolds and minimal folds at usable success rates, but those rates are still measured in percent of designs tested. We therefore design panels, filter them aggressively, and are explicit about the numbers involved.

Predicted fold with scored substitution sitesΔΔG scored per position · functional sites protected
Schematic: substitutions are scored at every position for stability and function, with catalytic and binding residues protected from redesign.

Key Advantages

01

Backbone Generation Then Sequence Design

Structure is generated first and sequence designed onto it, which produces folds matched to the functional requirement rather than borrowed from a natural protein.

02

In Silico Filtering Before Expression

Designs are filtered by structure prediction self-consistency, predicted confidence, interface metrics and stability, which is what raises experimental success rates from negligible to workable.

03

Motif Scaffolding Supported

A functional motif — an epitope, a binding loop, a catalytic arrangement — can be held fixed while a new scaffold is built around it to present it correctly.

04

Expression Realism Considered

Designs are screened for aggregation propensity, disulfide handling and expression-relevant features, since a design that cannot be produced is of no use.

Where This Service Is Used

Designing novel binders against a defined target surface
Building scaffolds that present an epitope correctly for vaccine or reagent applications
Creating miniproteins as alternatives to antibodies for imaging or delivery
Designing symmetric assemblies, nanocages or oligomeric scaffolds
Generating stable scaffolds to carry a functional motif that is unstable in isolation

Methods and Techniques Applied

Definition of the design objective: target surface, motif geometry, symmetry or fold requirement
Backbone generation with diffusion or hallucination methods under the stated constraints
Sequence design onto the generated backbones with fixed-backbone design methods
Self-consistency filtering: predicting the structure of each designed sequence and comparing it with the intended backbone
Interface, stability and packing assessment, with molecular dynamics for the leading designs
Expression-risk screening and selection of the panel to be synthesised and tested

What We Need From You

Target structure and the surface to be bound, or the motif and geometry to be scaffolded
Functional requirements: affinity, specificity, stability, size limits, oligomeric state
Expression system available, since it constrains disulfides, glycosylation and construct design
The number of designs you can express and screen, which determines panel size

What You Receive

Designed sequences with structural models and per-design filtering metrics
Self-consistency and confidence analysis for every delivered design
Interface analysis for binder designs, showing the intended interactions
Expression construct suggestions including tags, linkers and boundaries
Ranked testing order with a realistic statement of expected success rates

What We Compute and Report

Designed sequences with predicted structures and per-design filtering metrics
Self-consistency between the designed sequence and the intended backbone, in ångströms
Interface metrics for binder designs: buried area, shape complementarity, predicted contacts
Predicted stability and aggregation risk per design
Expression-risk indicators used to order the panel for testing

Interpretation and Limitations

Computational predictions prioritise hypotheses; they do not independently establish binding, biological activity, therapeutic efficacy, safety or clinical validity. Performance depends on input quality, target class, the structural evidence available and the applicability domain of the selected methods. Scores used for ranking are comparative devices and should not be read as measured quantities. All deliverables are for research use only and are not intended for diagnostic or therapeutic use.

Specifications

ItemSpecificationNotes
Designs delivered20–200 sequencesPanel size set by your screening capacity
Typical turnaround4–10 weeksGeneration, filtering and simulation included
Design typesBinders, scaffolds, assembliesIncluding motif scaffolding
Expected hit rateLow single-digit percent typicalTarget-dependent; stated per project

Service Workflow

Step 01

Scientific Consultation

We discuss the objective, the decision it supports and the data you hold. Nothing is quoted before we understand what the result has to answer.

Step 02

Feasibility Review

We check that the data, target class and available structural evidence can support the proposed approach, and say plainly where they cannot.

Step 03

Technical Proposal

Scope, methods, deliverables, timeline and price are confirmed in writing, together with the limitations we expect to report.

Step 04

Computation and QC

The analysis runs on pinned tool versions in a containerised environment, with quality checkpoints and method comparison where that is informative.

Step 05

Report and Follow-Up

You receive the ranked results, the documented methods, the limitations and a proposed validation plan, plus support in interpreting them.

Is This the Right Service for You?

Choose this service when

A small, stable binder is wanted as an alternative to an antibody
An epitope or functional motif must be presented on a purpose-built scaffold
Screening capacity exists for a designed panel rather than a single construct

Consider another service when

An existing protein needs stabilising rather than replacing
Protein Stability & Thermostability Engineering
An antibody format is acceptable and more precedented
Full-Length IgG Antibody Design

What Goes Wrong, and How We Handle It

The failure modes that produce confident-looking results which do not survive the next experiment. Each one is designed against rather than discovered afterwards.

Expected hit rates are stated before the project starts and panel size is set from them, not from the most favourable paper.

Case Studies

The situation
The team needed a small binder for an imaging application where an antibody was too large.
What the work involved
Backbones were generated against the target patch, sequences were designed onto them, self-consistency and interface metrics were used to filter aggressively, and the survivors were simulated briefly.
What came back
Ninety-six designs selected from several thousand generated, delivered with per-design metrics and expression construct suggestions, and with the expected success rate stated up front.

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.

Questions We Are Asked Before Scoping

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 in Touch
about De Novo Protein Design

Tell us about the target, the data you hold and the decision the result needs to support. A scientist reviews every enquiry and replies within one business day.

Feasibility reviewed before any scope or price is fixed
Methods, parameters, confidence and limitations in every report
Confidentiality agreement available before data is shared

Submitting opens your email client with the enquiry addressed to service@icdmo.com.