De Novo Allosteric Protein Switches

AI-Driven Biosensor Design

Design allosteric switches and ligand-binding domains from first principles using AI. No natural template required. Create custom biosensors for detection of small molecules, peptides, and proteins.

Key Capabilities

De Novo Design ML-Optimized Validated
Enginoma Structure Validated
Enginoma Backbone
Enginoma Sequence
Overview

Biosensor Design Solutions

Our AI-driven biosensor design platform enables the creation of allosteric protein switches from first principles—no natural template required. By leveraging machine learning-designed ligand binding domains and conformational entropy modulation, we engineer highly sensitive and specific biosensors for diverse applications.

De Novo Allosteric Switch Design

Generate entirely synthetic protein switches without relying on natural allosteric proteins. Machine learning models design novel conformational transitions responsive to target molecules.

Ligand Binding Domain Engineering

Design binding domains targeting specific molecules—from small metabolites to large proteins. Sub-nanomolar affinity achieved through ML-guided optimization.

Conformational Entropy Modulation

Engineer the thermodynamic coupling between ligand binding and functional output. Precise control over dynamic range and sensitivity.

Modular Sensor Architecture

Combine multiple binding domains for logic gate integration (YES, AND, OR gates). Create sophisticated detection schemes for complex analytical needs.

Core Technology

AI Design Pipeline

State-of-the-art machine learning and protein design algorithms integrated into a seamless workflow

Ligand Binding Domain Design

ML-designed binding domains that target specific molecules—from small metabolites to large proteins. No natural template required.

Capabilities
  • Small molecule binders (steroids, drugs)
  • Peptide recognition domains
  • Protein-protein interaction sensors
  • Sub-nanomolar affinity design

Allosteric Switch Engineering

Inverse the flow of information through designed protein switches. Ligand binding triggers functional output through thermodynamic coupling.

Mechanisms
  • Conformational entropy modulation
  • Lock-and-key protein association
  • Split-protein reconstitution
  • FRET-based readout systems

Validation & Optimization

Enginoma Structure validation ensures designed proteins fold correctly. ML models predict and optimize dynamic range and sensitivity.

Quality Metrics
  • pLDDT confidence scores
  • Binding affinity prediction (Kd)
  • Dynamic range optimization
  • Experimental validation
Design Modes

Versatile Sensor Architectures

Multiple design strategies for different detection needs and output formats

Circularly Permuted Design

Single-component allosteric switches

Insert circularly permuted binding domains into reporter proteins (beta-lactamase, dehydrogenases, luciferases) to create single-component sensors with dose-dependent response.

  • Wide dynamic range
  • Nanomolar affinity detection
  • Solution-based readout

Lock-and-Key Assembly

Modular two-component sensors

Design lock proteins that associate with key binders upon target binding. Reconstitute split reporters (luciferase, fluorescent proteins) for signal generation.

  • High sensitivity detection
  • Strong signal enhancement
  • Broad analyte range

Fluorescent Protein Sensors

Real-time imaging and detection

Engineer GCaMP-like calcium indicators, neurotransmitter sensors, and fluorescent biosensors with optimized kinetics and dynamic range using ML-guided mutagenesis.

  • Enhanced fluorescence brightness
  • Faster response kinetics
  • Genetically encodable

Transcription Factor Sensors

Whole-cell biosensing systems

Design allosteric transcription factors for metabolite detection and dynamic pathway regulation. ML-guided DBTL optimization for context-dependent performance.

  • Metabolite-responsive circuits
  • Dynamic range tuning
  • Cell-based screening
Applications

Industry Applications

AI-designed biosensors for diagnostics, research, and industrial monitoring

🏥

Clinical Diagnostics

Cardiac biomarkers (Troponin I), hormone detection (Cortisol, 17-OHP), cancer biomarkers

🧠

Neuroscience

Neurotransmitter sensors (Dopamine, Serotonin), calcium indicators, neural activity monitoring

🎩

Drug Discovery

High-throughput screening, compound detection, ADME-TOX assessment

🌍

Environmental Monitoring

Toxin detection, pathogen sensing, pollutant monitoring

🏭

Industrial Bioprocessing

Metabolite tracking, fermentation monitoring, quality control

🧬

Synthetic Biology

Dynamic pathway regulation, logic gates, cell-based biosensors

🔬

Research Tools

Protein-protein interaction detection, real-time signaling monitoring

📱

Point-of-Care Devices

Wearable sensors, paper-based assays, portable diagnostics

Process

How We Work

1

Target Definition

Define target molecule, desired detection range, and output format requirements

2

AI Design

Generate binding domains and allosteric switch designs using ML models

3

Computational Screening

Validate structures and predict binding affinity and dynamic range

4

Experimental Validation

Clone, express, and characterize sensor performance

References

Scientific Foundation

Our biosensor design platform is built on peer-reviewed research and validated methodologies

1

Watson, J.L. et al. De novo design of protein structure and function with Enginoma Backbone. Nature 620, 1089-1100 (2023). https://doi.org/10.1038/s41586-023-06415-8

2

Chen, J., Vishweshwaraiah, Y.L. & Dokholyan, N.V. Design and engineering of allosteric communications in proteins. Current Opinion in Structural Biology 72, 102334 (2022). https://doi.org/10.1016/j.sbi.2022.102334

3

Yin, R., Feng, B.Y., Varshney, A. & Pierce, B.G. Benchmarking Enginoma Structure for protein complex modeling reveals accuracy determinants. Protein Science 31, e4379 (2022). https://doi.org/10.1002/pro.4379

4

Wait, S.J., Rappleye, M., Lee, J.D., Goy, M.E., Smith, N. & Berndt, A. Machine learning-guided engineering of genetically encoded fluorescent calcium indicators. Nature Computational Science 4, 224-236 (2024). https://doi.org/10.1038/s43588-024-00611-w

FAQ

Frequently Asked Questions

The Enginoma platform supports detection of small molecules (steroids, metabolites, drugs), peptides (hormones, cytokines), and proteins (antibodies, receptors, toxins). We have successfully designed sensors for cortisol, 17alpha-hydroxyprogesterone, Bcl-2, Her2, Botulinum neurotoxin, cardiac Troponin I, and SARS-CoV-2 RBD.

Detection limits vary by target and application requirements. Our integrated design and validation workflow enables optimization for specific sensitivity and dynamic range needs.

Yes. Genetically encodable sensors (GCaMP-like indicators, luciferase-based switches) can be expressed in cells for real-time monitoring. Whole-cell biosensors based on transcription factors are also available for cell-based detection and screening applications.

The project timeline varies based on complexity, target molecules, and required validation scope. Contact us for a detailed project plan tailored to your specific needs.

Yes. Our integrated platform includes full wet lab validation services: protein expression, purification, functional characterization, binding assays (ITC, SPR), and performance optimization.

Design Your Biosensor Today

Transform your detection needs into reality with AI-designed allosteric switches. Contact us to discuss your target molecule and detection requirements.