Yeast Display Library Planner
Size combinatorial libraries against the yeast transformation ceiling, pick a codon scheme that covers the diversity you actually need, and calculate NGS depth for multi-round sort experiments. Catch impossibility flags before they become burned synthesis budget.
Free to use. Export a scoping-ready plan as CSV or PDF.
Built for teams scoping scFv, VHH, and alternative scaffold libraries for yeast surface display campaigns.
From scaffold description to scoping-ready plan
Describe your scaffold
Input the parent sequence, diversified positions, and type of diversity (full NNK scan, focused alphabet, trimer mix, or custom set).
Pick a codon scheme
Compare NNK, NNS, NNN, and trimer libraries against amino acid coverage, stop-codon frequency, and S. cerevisiae codon bias.
Size library and NGS
Library-size math against the yeast transformation ceiling, then Poisson-based NGS coverage calculations for each sort round.
Export a plan
Download a scoping-ready CSV or PDF with theoretical diversity, achievable diversity, sort strategy, and NGS read budget.
Five calculations behind the plan
Every output in the Library Planner traces to an explicit, inspectable calculation. Parameters are editable, assumptions are shown, and each section cites the statistical approach so a reviewer can reproduce the plan or adjust for their own platform.
Library complexity math
Compares NNK, NNS, and trimer library combinatorics against the yeast transformation ceiling of roughly 10^8 unique variants. A 20-position NNK scan is 32^20, or about 10^30 theoretical sequences, far beyond what any yeast library can sample. The planner flags when theoretical diversity exceeds practical coverage and suggests focused alternatives.
Codon bias analysis
Weights codon choices against the S. cerevisiae tRNA pool and rare-codon penalties. Surfaces cases where a nominally balanced codon scheme produces under-expressed variants due to translational stalling, and recommends trimer or optimized mixes where the bias penalty is steep.
NGS read depth
Poisson-based coverage confidence for pre-sort and post-sort NGS. Calculates the read depth required to recover a given variant at a target confidence level across sort rounds, so sequencing is budgeted against enrichment expectations rather than guessed.
Sort strategy
Suggests a MACS-then-FACS round sequence with decreasing target concentrations per round. Starting stringency, round count, and concentration ramp are fit to library size, expected binder frequency, and desired affinity discrimination.
Failure-mode detection
Raises impossibility flags when a plan cannot physically work. Example: 20 NNK-randomized positions encode 32^20, about 10^30 combinations, versus the 10^8 yeast transformation ceiling, a gap of roughly 22 orders of magnitude. The planner surfaces these conflicts up front, before synthesis orders go out.
Plan the library before you buy the DNA
Most yeast display campaigns that underperform were undercooked at the planning stage. A diversification strategy that looks reasonable in a slide deck often turns out to be 10^15 variants too large for yeast, or 10^3 variants too small to contain a single binder at useful frequency. Codon bias, NGS budgets, and sort strategy are all decided before any cell is transformed.
The Library Planner formalizes these decisions in one place. Run it before gene synthesis, before a sort plan is finalized, or any time a reviewer asks how the library size was picked.
Scoping a VHH library before committing to synthesis and transformation
Comparing CDR-focused versus full-surface diversification for an scFv
Planning NGS read depth and sequencing budget for a multi-round sort
Evaluating whether a design pool from BindCraft or RFdiffusion fits on yeast
Sizing a saturation library for affinity maturation of an existing lead
From a plan to a screened library
Once the library is planned, the next step is either running it in-house with a display partner or validating computational designs on yeast before committing further.
Run the library on yeast
High-throughput yeast surface display CRO services for scFv, VHH, nanobody, and custom scaffold libraries. FACS and MACS selection with NGS-resolved hit calling. Bring your planned library, or scope one together.
See Yeast Display Services → Flagship programComputational + display validation
The AI Binder Sprint pairs de novo design across RFdiffusion, BindCraft, and Boltzgen with yeast display validation. Designed pools are sized against the same yeast transformation ceiling you just planned against.
See the AI Binder Sprint →Plan your next library
The Yeast Display Library Planner is free. Enter your scaffold, diversification, and target KD, and get a scoped plan back in seconds. For a library you need to build and screen, our team can take it end to end.