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Designs covalent inhibitors and warheads targeting cysteine (most common, 98% of covalent drugs), lysine, serine, threonine, tyrosine, and aspartate residues, with explicit handling of warhead reactivity (acrylamide, chloroacetamide, vinyl sulfone, sulfonyl fluoride, fluorosulfate, aldehyde, boronate, nitrile), reversibility (kinact/Ki, t_residence), glutathione (GSH) stability, intrinsic reactivity assays, and covalent docking (DOCKovalent, GOLD, HCovDock). Use when designing covalent inhibitors for targeted covalent inhibition (TCI), KRAS G12C-style approaches, or rationalizing covalent SAR.

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Infer orthologous genes and gene families across species using OrthoFinder3 (HOG-based phylogenetic orthology), SonicParanoid2, Broccoli, ProteinOrtho, OMA / FastOMA hierarchical orthologous groups, eggNOG-mapper, JustOrthologs, and TOGA whole-genome-alignment orthology. Use when building single-copy ortholog sets for phylogenomics, classifying co-orthologs and in/out-paralogs after gene duplication, propagating functional annotation via orthology with awareness of the ortholog conjecture, distinguishing speciation from duplication via gene-tree species-tree reconciliation, computing Quest-for-Orthologs benchmark performance, or running synteny-aware ortholog detection in WGD-affected lineages.

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Discover RBP binding motifs from CLIP-seq peaks or single-nucleotide crosslink sites using HOMER, MEME/STREME, kpLogo, mCross (CL-position-registered motifs), PEKA (positional k-mer enrichment), RBPamp (affinity), and RNA Bind-n-Seq (RBNS) cross-validation. Use when characterizing RBP sequence specificity, registering motifs to crosslink positions, validating in vivo CLIP motifs against in vitro RBNS Kd, reconciling motif disagreements across tools, or correcting for the uracil crosslinking bias that contaminates raw CLIP motif logos.

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Batch effect correction for CRISPR screens covering ComBat empirical-Bayes, RUV, SVA, control-sgRNA normalization, and the model-based alternative of including batch as a covariate in MAGeCK MLE or Chronos. Covers screen-specific batch sources (passage cohort, library lot, infection day, sequencing run, Cas9 lot, FBS lot), PCA + variance-decomposition diagnostic to decide if correction is needed, when correction harms biology by over-correcting condition into batch, limma removeBatchEffect for visualization-only correction, and relationship to multi-condition design matrices. Use when combining screens for joint analysis, when passage cohort confounds biology, when DepMap-style panels need Chronos with batch covariates, when picking ComBat vs RUV, or when correction harms biology and should be replaced with explicit covariate modeling.

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Analyzes base-editing screens for variant function. Covers library design (Sanson 2020 GRACE, Hanna 2021 BRCA1/2 SNV scanning, Cuella-Martin 2021), CBE vs ABE chemistry choice (BE3/BE4 vs ABE7.10/ABE8.20/ABE8e), editing-window math (positions 4-8 from PAM-distal end, wider for ABE8e), bystander-edit quantification and the variant-call ambiguity it creates, sgRNA-efficiency filtering before hit calling, indel byproduct interpretation, the substitution-vs-indel diagnostic, variant annotation against ClinVar / COSMIC, and the Broad be-validation-pipeline. Use when designing a BE variant screen, choosing CBE vs ABE for a specific edit, interpreting bystander-confounded hits, distinguishing functional signal from indel artifact, integrating CRISPResso2 output with screen scoring, or deciding BE vs PE for SNV installation.

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Designs experiments to minimize and account for batch effects using balanced layouts and blocking strategies. Use when planning multi-batch experiments, assigning samples to sequencing lanes, or designing studies where technical variation could confound biological signals.

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Design guides for cytosine and adenine base editing using editing window optimization and BE-Hive outcome prediction. Select optimal positions for C-to-T or A-to-G conversions without double-strand breaks. Use when designing base editor experiments for precise nucleotide changes.

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Protein design quality control, filtering thresholds, and ranking guidance. Use this skill when: (1) Evaluating design quality for binding, expression, or structure, (2) Setting filtering thresholds for pLDDT, ipTM, PAE, (3) Checking sequence liabilities (cysteines, deamidation, polybasic clusters), (4) Creating multi-stage filtering pipelines, (5) Computing PyRosetta interface metrics (dG, SC, dSASA), (6) Checking biophysical properties (instability, GRAVY, pI), (7) Ranking designs with composite scoring. This skill provides research-backed thresholds from binder design competitions and published benchmarks.

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Analyze DNA/RNA/protein sequences. Use when the user provides a sequence and asks for analysis, translation, GC content, ORFs, motifs, restriction sites, or primer design. Triggers on "sequence", "translate", "GC content", "ORF", "primer", "restriction", "complement", "reverse complement".

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Proteina-Complexa flow-based protein backbone generation with fold-conditioned sampling guidance. Use this skill when: (1) Generating de novo protein backbones with hierarchical fold conditioning, (2) Exploring long-chain backbone generation beyond standard diffusion baselines, (3) Using NVIDIA Proteina-style flow matching workflows for controllable backbone design, (4) Comparing flow-based backbone generation against RFdiffusion or BoltzGen, (5) Prototyping fold-guided backbone campaigns before sequence design. This skill is based on the public NVIDIA Digital Bio Proteina project and uses "Proteina-Complexa" as the BioClaw-facing skill label. For sequence design after backbone generation, use proteinmpnn or solublempnn. For QC thresholds, use protein-design-qc.

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Bulk transcriptomics differential expression with count-aware modeling, design validation, contrast handling, thresholded exports, and publication-ready DE figures.

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Guidance for cell-free protein synthesis (CFPS) optimization. Use when: (1) Planning CFPS experiments, (2) Troubleshooting low yield or aggregation, (3) Optimizing DNA template design for CFPS, (4) Expressing difficult proteins (disulfide-rich, toxic, membrane).

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End-to-end binder design using BindCraft hallucination. Use this skill when: (1) Designing protein binders with built-in AF2 validation, (2) Running production-quality binder campaigns, (3) Using different design protocols (fast, default, slow), (4) Need joint backbone and sequence optimization, (5) Want high experimental success rate. For backbone-only generation, use rfdiffusion. For QC thresholds, use protein-qc. For tool selection guidance, use binder-design.

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Cell-free protein synthesis (CFPS) planning and optimization guidance. Use when: (1) Planning CFPS experiments, (2) Troubleshooting low yield or aggregation, (3) Optimizing DNA template design for CFPS, (4) Expressing difficult proteins (disulfide-rich, toxic, membrane).

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Guidance for choosing the right protein binder design tool. Use this skill when: (1) Deciding between BoltzGen, BindCraft, or RFdiffusion, (2) Planning a binder design campaign, (3) Understanding trade-offs between different approaches, (4) Selecting tools for specific target types. For specific tool parameters, use the individual tool skills (boltzgen, bindcraft, rfdiffusion, etc.).

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Binder design campaign planning, monitoring, and troubleshooting. Use this skill when: (1) Planning a complete binder design campaign, (2) Converting high-level goals into runnable pipelines, (3) Assessing campaign health and pass rates, (4) Diagnosing why designs are failing QC, (5) Estimating time, cost, and expected yields, (6) Selecting between design tools for a specific target. This skill orchestrates the other protein design tools. For individual tool parameters, use the specific tool skills.

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Solubility-optimized protein sequence design using SolubleMPNN. Use this skill when: (1) Designing for E. coli expression, (2) Optimizing solubility of designed proteins, (3) Reducing aggregation propensity, (4) Need high-yield expression, (5) Avoiding inclusion body formation. For standard design, use proteinmpnn. For ligand-aware design, use ligandmpnn.

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Design protein sequences using ProteinMPNN inverse folding. Use this skill when: (1) Designing sequences for RFdiffusion backbones, (2) Redesigning existing protein sequences, (3) Fixing specific residues while designing others, (4) Optimizing sequences for expression or stability, (5) Multi-state or negative design. For backbone generation, use rfdiffusion or bindcraft. For ligand-aware design, use ligandmpnn. For solubility optimization, use solublempnn.

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Boltz-1 / Boltz-2 structure prediction for proteins, complexes, and ligand-aware validation. Use this skill when: (1) Predicting protein complex structures, (2) Validating designed binders, (3) Need open-source alternative to AF2, (4) Predicting protein-ligand complexes, (5) Using local GPU resources. For QC thresholds, use protein-design-qc. For AlphaFold2 prediction, use alphafold2-multimer. For Chai prediction, use chai1-structure-prediction.

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AlphaFold2 / AlphaFold-Multimer structure prediction for validation and confidence scoring. Use this skill when: (1) Validating designed sequences fold correctly, (2) Predicting binder-target complex structures, (3) Calculating confidence metrics (pLDDT, pTM, ipTM), (4) Self-consistency validation of designs, (5) Multi-chain complex prediction with AlphaFold-Multimer. For faster single-chain prediction, use esm2-sequence-scoring. For QC thresholds, use protein-design-qc.

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Goal-oriented binder design campaign planning and health assessment. Use this skill when: (1) Planning a complete binder design campaign, (2) Converting high-level goals into runnable pipelines, (3) Assessing campaign health and pass rates, (4) Diagnosing why designs are failing QC, (5) Estimating time, cost, and expected yields, (6) Selecting between design tools for a specific target. This skill orchestrates the other protein design tools. For individual tool parameters, use the specific tool skills.

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Fetch and analyze protein structures from RCSB PDB. Use this skill when: (1) Need to download a structure by PDB ID, (2) Search for similar structures, (3) Prepare target for binder design, (4) Extract specific chains or domains, (5) Get structure metadata. For sequence lookup, use uniprot. For binder design workflow, use binder-design.

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End-to-end guidance for protein design pipelines. Use this skill when: (1) Starting a new protein design project, (2) Need step-by-step workflow guidance, (3) Understanding the full design pipeline, (4) Planning compute resources and timelines, (5) Integrating multiple design tools. For tool selection, use binder-design. For QC thresholds, use protein-qc.

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Chai-1 structure prediction for protein complexes and design validation. Use this skill when: (1) Predicting protein-protein complex structures, (2) Validating designed binders, (3) Predicting protein-ligand complexes, (4) Using the Chai API for high-throughput prediction, (5) Need an alternative to AlphaFold2. For QC thresholds, use protein-design-qc. For AlphaFold2 prediction, use alphafold2-multimer. For ESM-based analysis, use esm2-sequence-scoring.

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