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An antibody's specificity and affinity are largely determined by its complementarity-determining regions (CDRs). Through structure-guided, precise CDR diversification, we systematically explore the sequence space while preserving the antibody's structural stability and affinity—capturing a broader sequence diversity of same-function antibodies with smaller, higher-quality libraries. The system offers sequence- and structure-based dual-branch workflows, and uses energy scoring plus position-level protection strategies to deliver a library-ready, high-quality candidate set.
Key Features
Why Is This Needed?
"Traditional CDR diversification relies on random mutagenesis or semi-rational design: random mutations generate many ineffective variants, burying truly valuable sequences among countless candidates; mutations without structural constraints easily disrupt antibody folding, causing poor expression or aggregation; and boosting hit rates often requires screening libraries of millions or even billions, making cost and timeline the bottleneck. What teams need is a smaller, higher-quality, structurally sound candidate library."
Key Advantages
Random mutations generate large numbers of ineffective variants, burying the truly valuable sequences among countless candidates.
Mutations without structural constraints easily disrupt antibody folding, leading to poor expression or aggregation.
Boosting hit rates requires screening libraries of millions or even billions, making cost and timeline the bottleneck.
Evaluates the impact of each mutation at the 3D protein-structure level, automatically identifying key antigen-contact residues and structural support sites, and quantifying mutation effects to narrow the search space.
Directed sampling based on physicochemical properties and evolutionary information; supports position-level protection (avoid/include) and configurable N/C-terminal extensions to precisely control mutation positions and CDR boundaries.
Supports the four mainstream numbering schemes—Kabat, Chothia, IMGT, AHO—plus the ALL mode (union of all four), ensuring compatibility with diverse databases and literature.
The sequence branch runs structure prediction and mutation design directly from sequences with no manual modeling; the structure branch leverages an existing complex structure for more precise energy calculations and site-specific analysis.
How It Works
Two branches—sequence and structure—auto-identify CDR regions, predict/refine structures, then drive mutation design and ranking with energy scoring to deliver a library-ready, high-quality candidate set.
Input antibody and antigen sequences → structure prediction → energy scoring → mutation design. Ideal for early-stage projects with sequence information only—fully automated, no manual modeling required.
Input an antibody–antigen complex structure → structure refinement and analysis → saturation mutagenesis scan → precise scoring. Suited to projects with a crystal structure or high-quality model, providing more accurate energy calculations and site-specific analysis.
Input sequence / structure → multi-scheme CDR auto-annotation (with protection strategy) → structure prediction / refinement → energy-scoring-driven mutation design → Top candidate sequences and ranking per CDR
Report
The following screenshots are excerpts from a CDR Diversity Design report, demonstrating the full computational workflow from parental sequence characterization to CDR mutation design and candidate sequence evaluation.
Use Cases
Best suited when you have an affinity-qualified lead antibody and want to explore sequence diversity through CDR optimization ahead of library screening.
Affinity maturation focuses on strengthening binding to a specific antigen, typically via saturation mutagenesis and ML-based mutation-effect prediction. CDR diversification focuses on exploring sequence diversity, generating a diverse variant library while preserving structural stability. The two are complementary: use CDR diversification to build the initial library, then affinity maturation to optimize the hits.
Antibody folding follows strict physicochemical rules, and random mutations are likely to break them, causing misfolding or aggregation. Structure-guided design uses energy calculations to pre-exclude these "dead-end" sequences, ensuring every variant in the library has a reasonable chance of folding correctly—substantially improving screening efficiency.
A single run can generate hundreds to thousands of candidate CDR sequences (Top 5–100 candidates per CDR; the combinatorial theoretical diversity across 6 CDRs can reach millions or more). The actual library size depends on the sequence-identity parameters and protection strategy. For wet-lab screening, we recommend combining the Top candidates of each CDR to build an appropriately sized library on demand.
~2 hours per run, priced at 12,888 credits / antibody / run.
Submit sequences or a complex structure, choose the numbering scheme and protection strategy, and receive a structurally sound, library-ready high-quality CDR candidate set for screening.