FoldEZ™ Platform

The FoldEZ™ Platform from Creative BioMart provides a robust solution for the efficient expression, purification, and refolding of membrane proteins—particularly G protein-coupled receptors (GPCRs) and ion channels. Utilizing a proprietary E. coli –based system, FoldEZ™ dramatically enhances recombinant protein yield, purity, and functionality. With success rates exceeding 75% across over 200 membrane protein targets, FoldEZ™ empowers researchers with reliable, scalable access to high-quality proteins for drug discovery, antibody development, and structural biology applications.

Background: What Is FoldEZ™ Platform

Membrane proteins, including GPCRs and ion channels, are essential components of cellular signaling and represent more than 50% of all current drug targets. However, their low natural abundance, structural complexity, and hydrophobicity make large-scale production of functional proteins a major technical challenge.

To address these challenges, Creative BioMart developed the FoldEZ™ Platform, an integrated expression and refolding solution tailored for membrane proteins. This proprietary system combines optimized expression strategies, solubilization conditions, and a multi-step refolding protocol that mimics the native lipid environment, ensuring correct folding and biological activity. FoldEZ™ supports a range of expression hosts—including E. coli, insect, and mammalian systems—and is compatible with both tagged and untagged protein formats.

Using advanced screening algorithms and biophysical monitoring, the platform precisely controls folding kinetics and prevents aggregation during purification. The result is a high yield of functional, structurally intact membrane proteins ready for downstream applications such as structural biology, ligand screening, antibody development, and cryo-EM or X-ray crystallography studies.

By transforming the traditionally challenging process of membrane protein production into a reliable and scalable workflow, the FoldEZ™ Platform empowers researchers and pharmaceutical developers to accelerate discovery and reduce development risk across a wide range of therapeutic programs.

What Our FoldEZ™ Platform Deliver

Creative BioMart provides comprehensive services through the FoldEZ™ Platform, including:

• Custom expression of challenging membrane proteins, including GPCRs, ion channels, and transporters.
• High-yield recombinant protein production using an optimized E. coli system.
• Purification and refolding of inclusion body-derived proteins into functional, correctly folded conformations.
• Parallel production of multiple protein variants or targets for comparative studies.
• Analytical validation, including activity assays, ligand binding, and structural confirmation.
• Scalable production for research, preclinical, or early drug discovery applications.

Service Workflow

	Step	Description
1	Gene Cloning and Construct Design	Target genes are cloned into optimized expression vectors tailored for efficient aggregation and refolding.
2	Expression in E. coli	Proteins are expressed in inclusion bodies, ensuring exceptionally high yield and controlled aggregation.
3	Isolation and Solubilization	Inclusion bodies are isolated and solubilized under carefully optimized conditions to preserve refolding potential.
4	Purification and Refolding	Proprietary refolding protocols restore the protein’s native conformation and functional integrity.
5	Functional Validation	Each refolded protein is analyzed for activity, stability, and binding properties to confirm biological relevance.
6	Delivery and Reporting	Comprehensive data reports and validated protein samples are delivered to the client for downstream applications.

Service Features

• Expression Host: E. coli
• Yield: Typically 5–50 mg per liter of culture medium
• Performance: Up to 10,000-fold higher yield than conventional expression systems
• Success Rate: Over 75% success in expression and refolding of new targets
• Validated Targets: Over 200 GPCRs and ion channels successfully expressed
• Applications: Structural biology; ligand screening and drug discovery; antibody generation; functional reconstitution assays

Why Choose Our FoldEZ™ Platform

Proprietary Technology: FoldEZ™ represents a unique, proven solution for overcoming the bottlenecks of membrane protein expression.

Exceptional Yields: Achieve milligram-level quantities of functional protein, even for low-abundance targets.

High Success Rate: More than 75% success across hundreds of diverse membrane proteins.

Expert Scientific Team: Our specialists bring deep expertise in protein chemistry, folding, and membrane biophysics.

Flexible, Customizable Solutions: Tailored workflows to meet project-specific requirements and timelines.

Accelerated Discovery: Parallelized expression enables rapid evaluation of multiple targets or variants simultaneously.

Case Studies and Success Stories

Case 1: GPCR expression and functional refolding for antibody discovery

Background:
A pharmaceutical client was developing monoclonal antibodies targeting a low-abundance G protein-coupled receptor (GPCR) implicated in inflammatory disease. Traditional mammalian and insect expression systems yielded insufficient amounts of functional receptor, hindering antibody screening and structural validation.
Approach:
Creative BioMart implemented the FoldEZ™ Platform to overcome expression limitations. The target GPCR gene was cloned into a proprietary E. coli vector optimized for inclusion body formation. After large-scale bacterial expression, the aggregated receptor protein was solubilized, purified, and subjected to a multi-step refolding process. Refolding buffers and redox conditions were carefully optimized to restore native tertiary structure and ligand-binding capability.
Results:
The process produced 40 mg/L of functional receptor, representing a dramatic yield improvement over traditional cell-based system. Ligand-binding assays confirmed correct folding and pharmacological activity, with an affinity profile consistent with native receptor behavior. The functional GPCR enabled the client to successfully perform antibody screening and epitope mapping using the refolded protein as a target antigen.
Impact:
By employing FoldEZ™, the client reduced their development timeline by nearly 50%, achieved reproducible large-scale protein production, and identified several high-affinity antibody candidates for preclinical evaluation.

Case 2: Ion channel production for structural and functional studies

Background:
An academic research group investigating a voltage-gated ion channel involved in neurological disorders required purified, functional protein for cryo-electron microscopy (cryo-EM) and ligand-binding analysis. However, attempts using mammalian and yeast systems produced unstable or misfolded protein, preventing high-resolution structure determination.
Approach:
The FoldEZ™ Platform was used to express the ion channel in E. coli as inclusion bodies, ensuring high accumulation of recombinant material. The protein was subsequently purified and refolded using Creative BioMart’s proprietary oxidative folding system designed to reconstitute membrane proteins into functional states. The refolded ion channel was then incorporated into lipid nanodiscs for biophysical characterization.
Results:
The method yielded over 30 mg/L of properly folded ion channel protein with stable electrophysiological properties confirmed by planar lipid bilayer assays. The protein’s structure was successfully resolved at 3.4 Å resolution using cryo-EM, revealing new conformational features critical to its gating mechanism.
Impact:
The high-quality protein obtained through FoldEZ™ enabled the research group to publish a landmark study and identify a previously unrecognized binding pocket, which has since become the focus of ongoing drug discovery efforts targeting neurological dysfunction.

Customer Testimonials on FoldEZ™ Platform

“Our team collaborated with Creative BioMart to express a challenging Class B GPCR target for therapeutic antibody development. Using their FoldEZ™ Platform, they delivered functional protein with verified ligand-binding activity and excellent batch-to-batch consistency. The project moved from gene synthesis to validated antigen in under eight weeks—far faster than we anticipated. Their scientific team maintained transparent communication throughout and provided insightful data analysis that guided our immunization strategy.”

— Director of Antibody Discovery | Mid-size Biopharmaceutical Company

“We engaged Creative BioMart for the expression and refolding of a neuronal ion channel that had failed in both insect and mammalian systems. Their FoldEZ™ Platform produced over 35 mg/L of correctly folded protein, enabling us to complete our electrophysiology and cryo-EM studies without further optimization. The quality of the material was outstanding—stable, active, and reproducible. Their expertise in handling difficult membrane proteins saved our program months of troubleshooting.”

— Principal Scientist, Structural Biology | Neuroscience Research Institute

“Creative BioMart’s FoldEZ™ Platform was instrumental in our early-stage GPCR validation efforts. We needed multiple receptor variants expressed rapidly for ligand-binding assays, and their parallel expression format delivered all six constructs within a single project cycle. The team’s ability to refold and confirm functionality across variants was particularly impressive. Their technical reports were thorough and publication-ready, which made internal review and follow-up experiments seamless.”

— Head of Molecular Pharmacology | Global Pharmaceutical Company

“Our collaboration with Creative BioMart focused on producing a viral envelope glycoprotein that had proven extremely unstable in conventional expression systems. The FoldEZ™ Platform not only yielded a properly folded, homogeneous protein preparation but also maintained its native conformation during purification and storage. The resulting material was key to generating high-resolution cryo-EM structures and developing neutralizing antibodies. The team’s technical depth and responsiveness made the entire process remarkably smooth.”

— Senior Scientist, Vaccine Discovery | Biotechnology Company

FAQs About Our FoldEZ™ Platform

• Q: What makes the FoldEZ™ Platform unique?

  A: FoldEZ™ uses a proprietary E. coli system that drives proteins into inclusion bodies, followed by optimized purification and refolding steps. This approach delivers up to 10,000× higher yield and faster turnaround than conventional membrane protein expression systems.

• Q: Which proteins can FoldEZ™ produce?

  A: FoldEZ™ specializes in GPCRs, ion channels, and other challenging membrane targets such as transporters and receptors. Over 200 proteins have been successfully produced with a >75% success rate.

• Q: What yield and quality can I expect?

  A: Typical yields range from 5–50 mg/L, depending on the target. Each protein is confirmed to be properly folded and functional through standard activity and binding assays.

• Q: Can you express multiple protein variants in parallel?

  A: Yes. FoldEZ™ supports parallel expression of multiple constructs or variants—ideal for mutagenesis studies, structure-function analysis, or ligand screening.

• Q: How long does a project take?

  A: Most projects are completed within 6–12 weeks from gene sequence to validated protein, depending on complexity and analysis requirements.

• Q: Is FoldEZ™ scalable for larger production?

  A: Yes. FoldEZ™ is fully scalable—from pilot-scale research to preclinical production—without compromising yield or functionality.

• Q: What do I need to start a project?

  A: Just provide your gene sequence or cDNA, along with any background data. We’ll handle construct design, vector optimization, and feasibility assessment.

• Q: How is protein functionality verified?

  A: Each refolded protein is tested for correct folding and biological activity, such as ligand binding or conformational integrity, before delivery.

• Q: What support can I expect during the project?

  A: You’ll receive regular updates, detailed reports, and direct communication with our scientists throughout the entire process.

• Q: How can FoldEZ™ accelerate my research?

  A: FoldEZ™ enables rapid, reliable access to functional membrane proteins, speeding up structure studies, screening, and antibody discovery—while reducing development time and cost.

References:

• Löbbert A, Lorz N, Matthees ESF, Rößler P, Hoffmann C, Gossert AD. GPCR kinases phosphorylate GPCR C-terminal peptides in a hierarchical manner. Commun Biol. 2025;8(1):899. doi:10.1038/s42003-025-08301-7
• Tyedmers J, Mogk A, Bukau B. Cellular strategies for controlling protein aggregation. Nat Rev Mol Cell Biol. 2010;11(11):777-788. doi:10.1038/nrm2993