Eliminate unstable folds and host liabilities before ordering DNA.
Static structure confidence scores miss unclosed active sites, unpaired ER cysteines, glycan active-site occlusion, and thermal breathing. We audit candidate batches in explicit solvent and engineer clean, refolded variants ready for synthesis.
Explicit-solvent triage & host compatibility check on 20–50 designs.
Built for teams narrowing AlphaFold 3, Boltz-2, OpenFold 3, RFdiffusion, ProteinMPNN, or metagenomic candidate pools down to a high-confidence synthesis plate. Rather than applying arbitrary fixed RMSD cutoffs, every run includes matched intact and destabilized control structures (1.13 Å vs. 2.49 Å mean 330 K drift—a 1.36 Å separation in our pre-registered benchmark) alongside active-site distance checks to separate stable folds from designs that come apart under heat.
01 · You Provide
- 20–50 amino-acid FASTAs or predicted 3D structures (PDB/mmCIF)—up to 2,500 residues in a single local pass, 5,000+ residues via phase-matched window stitching (tested to 8,600 aa), or larger complexes on dedicated cloud GPUs.
- Intended expression host (e.g., E. coli cytosol, Pichia / Aspergillus / CHO secretion, or cell-free).
- Optional catalytic triad, cofactor, ligand pocket, or oligomeric interface residues to monitor.
- 1–2 known active benchmark sequences (or we select public structural controls).
02 · Computational Protocol
- Boundary & leader audit: checks miscalled start codons, signal peptides, pro-sequences, and truncated repeat or domain ends.
- Host disulfide & glycosylation audit: 3D separation of structural disulfides (≤7.5 Å Cα–Cα) from unpaired ER-retaining cysteines, plus active-site N-glycan occlusion.
- Explicit-water OpenMM MD: solvated, charge-neutralized 300 K and 330 K trajectories tracking local flexibility, pocket persistence, and oligomeric interface stability.
03 · Deliverable Package
- Per-candidate biophysical scorecard (CSV/JSON + executive PDF summary) separating pass, warning, and structural failure modes.
- 300 K & 330 K trajectory metrics, active-site distance distributions, and matched-control comparison bands.
- Equilibrated 3D coordinate snapshots (PDB/mmCIF) and complete OpenMM force-field & parameter logs.
| Package Tier | Cohort & Simulation Depth | Turnaround | Fixed Fee | |
|---|---|---|---|---|
| Triage Screen | 20–50 candidates; full sequence/host liability audit + 0.5 ns 300 K / 330 K explicit-water relaxation screen | 3–5 business days | $5,000 – $7,500 | Select tier → |
| Standard Screen | 20–50 candidate audit + 10 ns explicit-water MD at 300 K & 330 K across top 10–15 designs + controls | 5–7 business days | $7,500 – $9,000 | Select tier → |
| Extended Triplicate | Full cohort triage + triplicate 50 ns+ independent trajectories on 3–5 lead candidates | 7–10 business days | $8,500 – $10,000 | Select tier → |
Scrub ER cysteines, glycan traps, and PTM liabilities without breaking the fold.
When a promising enzyme or binder fails eukaryotic secretion or formulation stability due to exposed unpaired cysteines, N-X-S/T glycosylation sequons near the active site, Met/Trp oxidation hotspots, Asn-Gly deamidation, or host protease sites, naive point mutagenesis often collapses packing. We lock catalytic and interface coordinates while optimizing the surrounding sequence and verifying every variant by independent 3D refolding and explicit-water MD.
01 · You Provide
- 1–3 parent protein sequences or 3D models (monomer or symmetric homo-oligomer).
- Target expression pathway (e.g., Pichia Kex2 secretion, Aspergillus, CHO, or cytosolic bacterial expression) and formulation pH/temperature.
- Immutable residue list (catalytic triad, metal cage, epitope, or binding surface).
02 · Computational Protocol
- Disulfide-safe cysteine cleanup: preserves paired structural disulfides, lipoboxes, and catalytic cysteines while substituting exposed unpaired cysteines that stall secretion.
- Active-site-locked sequence redesign: simultaneously removes N-glycan traps, dibasic protease clips, deamidation/oxidation motifs, and aggregation-prone hydrophobic patches.
- Independent 3D refolding & water MD: every proposed variant is refolded from scratch without templates and checked in 300 K / 330 K explicit water.
03 · Deliverable Package
- 10–25 diversity-spaced, active-site-locked variant sequences with per-mutation biophysical rationale tables.
- Refolded 3D PDB models + explicit-water backbone and active-site stability comparisons against the wild-type parent.
- Related reading: Unpaired ER cysteines vs. structural disulfides →
| Package Tier | Optimization Scope | Turnaround | Fixed Fee | |
|---|---|---|---|---|
| Monomer Scaffold Optimization | 1 parent monomer; liability scrubbing + 10–25 independently refolded and MD-verified variants | 5–7 business days | $8,000 – $11,500 | Select tier → |
| Homo-Oligomer or Multi-Parent | Symmetric homo-oligomer interface-locked optimization or 2–3 related parent scaffolds | 6–8 business days | $11,500 – $15,000 | Select tier → |
Continue across the computational R&D lifecycle.
Construct Design & Clone Verification
Contingent repetitive gene synthesis rescue, raw-read broken ORF reconstruction, and ONT/HiFi clone integration audits.
Assay Video, Melting Curves & Plate Kinetics
Automated curves and figures from DSF melt exports, clearing and fluorescence time-lapses, thermal-camera plates, and 96-well freezing runs.
Patent-Clear Discovery & Sequence Audits
Low-identity 3D homolog & ASR panels, pre-filing claim & ST.26 audits, and SPPS miniprotein discovery.