ESMFold2-pipeline Project Setup

ESMFold2-pipeline is Ariax Bio's fourth design engine and the first Ariax workflow with first-class scFv design. It also supports miniproteins and VHH nanobodies. Every Ariax campaign includes Protenix v2 validation and structural templates.

Inputs

• Upload a PDB/mmCIF target structure or enter a four-character RCSB PDB ID.
• Ariax detects the target's author chain IDs. Select or deselect chains from
  the detected list instead of typing chain names manually.
• For each selected chain, optionally enter comma-separated hotspot residue
  numbers, such as 42,45, and author-numbered crop ranges such as
  1-180,190. The form checks these values against the loaded structure.
• Choose Miniprotein, VHH, or scFv. Miniproteins use a binder length; antibody designs use bundled structural frameworks.

All bundled VHH or scFv frameworks are used by default. Open the framework selector to exclude frameworks or choose a smaller subset. scFv options are paired VH→VL structural frameworks and cover both heavy- and light-chain CDR design. Custom framework sequences and templates are not supported in the first release.

Campaign size and ranking

Enter the number of designs directly; the form starts at 100. Ariax does not impose a campaign-size preset or absolute design-count maximum. Starting a campaign requires available credit, and every run uses a 100 GB local work disk with runtime disk monitoring.

ESMFold2-pipeline uses 150 optimization steps for every production campaign. This value is server-owned and is not a user setting. Final ranked results default to the top 100 and cannot exceed 100.

Validation

Protenix v2 validation is required on every run. By default, every design with ESMFold2 ipTM of at least 0.6 is validated. Advanced Settings exposes the ipTM gate and an optional validation top-k cap; leave top-k blank to validate everything above the gate.

Public ColabFold MSAs are enabled by default and can be switched off under Advanced Settings. For scFv, the public MSA applies to the target while the bundled structural framework supplies the binder template; scFv binder MSAs are not used. Structural templates always remain enabled, including when MSAs are off. Protenix itself and template use cannot be disabled.

Advanced settings

• Inversion model: Fast is the default; Fast Cutoff 2025, Cutoff 2025, and Experimental are available.
• Validation ipTM threshold: 0.6 by default.
• Validation top-k: blank means all designs above the threshold.
• Ranked results top-k: 100 by default and at most 100.
• Public ColabFold MSA: on by default.
• Framework contact penalty: VHH/scFv only and 0 by default.

Compute

ESMFold2-pipeline requires an 80 GB or larger GPU. Eligible classes are A100 80GB, H100, H200, RTX 6000 Pro Blackwell, B200, and B300. A100 40GB and all lower-memory GPUs are excluded. Choose Performance or Cost ranking to control how Ariax orders eligible offers. GPU availability varies by workflow and demand.

Monitoring, recovery, and downloads

The project page shows planning, ESMFold2 design, selection, Protenix v2 validation, ranking, and completion stages with the latest job's billing state. Campaign state is checkpointed so that a paused or interrupted run can restore its durable artifacts before continuing.

Completed projects provide individual visible result files and tar.gz archives for ESMFold2 outputs, Protenix v2 validation, ranked results, and diagnostics. Durable visible results and archives follow Ariax's current retention policy.