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Trusted by Leading Research & Pharma Institutions

Semirational Protein Design

Accelerate your protein engineering projects with our semirational design platform. By combining computational predictions with targeted mutagenesis, we deliver optimized proteins with enhanced stability, activity, and specificity for your specific applications.

AI-Powered Design
Structure-Guided
High Throughput
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Trusted by leading research and pharmaceutical institutions

Harvard
Pfizer
MIT
Roche
Stanford
Novartis

Why Choose Us

Structure-based hotspot identification
Multi-parameter optimization capability
Integrated functional screening
Expert consultation included

Hotspot Mapping

Identify critical residues for targeted mutagenesis

Library Design

Focused libraries with maximum diversity

Screening & Validation

High-throughput functional assays

Success Rate
85%+
Service Overview

Comprehensive Semirational Design Solutions

Our platform combines computational protein design with experimental validation for superior results.

Computational Analysis

Advanced structural modeling and sequence analysis to identify optimal mutation targets. Our algorithms analyze protein structures, evolutionary conservation, and functional networks to predict beneficial mutations.

  • Structure prediction and modeling
  • Hotspot residue identification
  • Stability and dynamics analysis

Library Construction

Precision-engineered mutant libraries with focused diversity. We design and construct saturation mutagenesis libraries at identified hotspots, maximizing the probability of finding improved variants.

  • Site-saturated mutagenesis
  • Combinatorial library design
  • Smart pooling strategies

Multi-parameter Optimization

Simultaneous optimization of stability, activity, selectivity, and expression levels.

Rapid Iteration

Efficient design-build-test cycles for accelerated protein engineering projects.

Flexible Applications

Adaptable workflows for enzymes, antibodies, receptors, and engineered proteins.

Ready to Optimize Your Protein?

Get a customized quote for your semirational design project.

Technology Platform

Advanced Design Technologies

State-of-the-art computational and experimental tools for superior protein engineering.

Structure Modeling

Advanced structural modeling and prediction tools to understand protein architecture and guide mutation selection for improved functional properties.

AlphaFold2 Rosetta

Hotspot Identification

Computational analysis of protein structures and sequences to identify residues with the highest impact on target properties for focused mutagenesis.

Evolutionary Energetic

Library Design

Smart library construction strategies including NNK, NDT, and codon-optimized approaches to maximize diversity while minimizing screening burden.

NNK/NDT Smart Pools

Design Validation

MD Molecular dynamics simulation
DDG Stability change prediction
MSA Evolutionary conservation analysis
COA Comprehensive design report

Screening Methods

HTS High-throughput screening assays
FACS Flow cytometry-based selection
DSS Droplet-based screening
MS Mass spec characterization
Specifications

Flexible Options for Diverse Needs

Comprehensive specifications to meet your protein engineering requirements.

Parameter Hotspot Analysis Library Design Full Service
Analysis Depth Structure + sequence Comprehensive End-to-end design
Hotspots Identified Up to 5 sites Up to 10 sites Unlimited
Library Size N/A Up to 10,000 variants Custom scale
Turnaround Time 2-3 weeks 3-5 weeks 6-12 weeks
Deliverables Analysis report Library + report Validated variants
Screening Included No Optional Yes
Workflow

Streamlined Process from Design to Delivery

Our proven 5-step workflow ensures quality and efficiency at every stage.

1

Requirements

Define target properties and constraints

2

Analysis

Structural and sequence analysis

3

Design

Mutation strategy and library design

4

Build

Library construction and validation

5

Screen

Functional screening and analysis

Applications

Diverse Applications Across Biotechnology

Our semirational design services support research and development in multiple fields.

Industrial Enzyme Optimization

Enhance enzyme performance for industrial applications including thermotolerance, pH stability, substrate specificity, and catalytic efficiency. Our platform accelerates enzyme engineering for real-world conditions.

  • Thermostability improvement
  • pH and solvent tolerance
  • Substrate specificity tuning
  • Activity and kcat optimization
20°C+
Thermal stability improvement

Antibody Humanization & Optimization

Improve antibody properties including humanization, affinity maturation, and stability optimization. Our computational tools predict and validate beneficial mutations for therapeutic development.

  • Human framework adaptation
  • CDR affinity maturation
  • Thermal stability enhancement
  • Expression yield optimization
10x+
Affinity improvement potential

Sustainable Industrial Biotechnology

Develop robust biocatalysts for sustainable manufacturing including biofuel production, bioremediation, and green chemistry applications. Our platform addresses real-world industrial challenges.

  • Solvent and inhibitor tolerance
  • Long-term operational stability
  • Broad substrate compatibility
  • Process condition adaptation
3x
Productivity improvement
Testimonials

What Our Clients Say

Trusted by researchers worldwide for quality and reliability.

"The semirational design approach significantly accelerated our enzyme optimization project. The hotspot identification was spot-on and we achieved a remarkable improvement in thermostability."

J
Lead Scientist
Biotechnology Company

"Excellent service and professional team. The consultation was thorough and the design recommendations were backed by solid computational analysis. Will definitely use again."

S
Research Director
Academic Research Institution

"The library design was exceptionally well thought out. Smart pooling reduced our screening effort by half while maintaining comprehensive coverage of the sequence space."

M
Principal Investigator
Pharmaceutical Company
Scientific Literature

Scientific Foundation

Our platform is backed by peer-reviewed research.

45 Citations

Rationally seeded computational protein design of α-helical barrels

Albanese KI, Petrenas R, Pirro F, et al. Nature Chemical Biology. 2024.

A combined rational design and computational method using validated coiled-coil assemblies as seeds to design α-helical barrel proteins with 70% success rate.

View DOI
68 Citations

Rational and Mechanistic Approaches for Improving Biocatalyst Performance

Phintha A, Chaiyen P. Chem Catalysis (Cell Press). 2022.

Review of rational and semirational design strategies for improving biocatalyst performance including protein stability, activity, and solubility.

View DOI
156 Citations

Making Enzymes Suitable for Organic Chemistry by Rational Protein Design

Reetz M. ChemBioChem. 2022.

Review of semirational directed evolution methods (CAST/ISM) and rational enzyme design for stereoselective enzyme engineering using Rosetta and machine learning tools.

View DOI
89 Citations

Protein Engineering Design from Directed Evolution to De Novo Synthesis

Xiong W, Liu B, Shen Y, Jing K, Savage TR. Biochemical Engineering Journal. 2021.

Comprehensive review of protein engineering strategies from directed evolution and semirational design to AI-assisted computational protein design methods.

View DOI
42 Citations

Rational Design of Enzyme Activity and Enantioselectivity

Multiple authors. Frontiers in Bioengineering and Biotechnology. 2023.

Review of rational design strategies for enzyme activity and enantioselectivity improvement using multiple sequence alignment, steric hindrance modification, and computational design.

View DOI
FAQ

Frequently Asked Questions

Find answers to common questions about our service.

Semirational design combines elements of both rational design (using structural and computational data) and random mutagenesis. It focuses mutations on specific residues identified as important (hotspots) rather than random mutagenesis across the entire sequence. This approach significantly increases the probability of finding improved variants while reducing screening burden compared to fully random approaches.
We use a multi-pronged approach combining structural analysis, evolutionary conservation, molecular dynamics simulations, and energy calculations. Key methods include: (1) Alanine scanning data when available, (2) B-factor and RMSF analysis from MD simulations, (3) Sequence alignment conservation scoring, (4) Rosetta/FoldX energy calculations, and (5) machine learning-based prediction tools. The most promising residues are prioritized based on their predicted impact on target properties.
Our platform can address a wide range of protein properties including: thermodynamic stability, catalytic activity and efficiency (kcat/Km), substrate specificity and selectivity, pH and temperature tolerance, solvent and inhibitor resistance, protein-protein interaction affinity, expression yield and solubility, and immunogenicity. Multi-parameter optimization is possible by prioritizing targets based on your specific application requirements.
We employ multiple library design strategies depending on your needs: (1) NNK/NDT codon randomization for complete coverage at single sites, (2) Smart pool strategies for combinatorial libraries, (3) Structure-guided amino acid selection based on predicted tolerance, (4) Ancestral sequence reconstruction for beneficial background mutations, and (5) Computational library design using protein language models. Our team will recommend the optimal strategy based on your target properties and screening capacity.
Yes, we offer comprehensive screening services as part of our full-service packages. We provide high-throughput screening methods including microtiter plate-based assays, FACS-based screening for surface display systems, droplet-based microfluidic screening, and next-generation sequencing-based fitness profiling (-deep mutational scanning). We can also work with your existing screening platform or develop custom assays for your specific applications.
Project timelines vary based on scope: Hotspot analysis alone: 2-3 weeks. Library design and construction: 3-5 weeks. Full-service design-build-screen: 6-12 weeks. The full workflow includes computational analysis, library construction, quality validation, and functional screening. Rush options are available for time-sensitive projects. Our team will provide a detailed project plan with milestones after the initial consultation.

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