Phase 1A / target review

Biological review packet for the frozen target set

Structured target-level caveats for using the 8-target SimpleFold-3B set as an operational viability benchmark without overclaiming biological generality.

Operational viability

8 / 8
All targets are acceptable for the bounded local-runtime claim.

Biological generality

blocked
The set is mixed and caveated, not biologically representative.

Needs review

human
External biological review is still pending before biological generality claims.

Decision

The Phase 1A set is suitable for a first-paper operational viability claim: SimpleFold-3B ran and scored across a frozen mixed-context set on an M3 Max workstation. It is not suitable for broad biological generality claims. The target mix is useful precisely because it includes clean X-ray cases, membrane/transport stress cases, long enzyme contexts, and complex-derived coverage probes.

Review Summary

BucketCount
Acceptable for operational viability6
Acceptable with coverage caveat1
Acceptable with context caveat1
Blocked for biological generality2

Target-Level Caveats

TargetContext classRecommendationCaveat
13CZ:Apaired membrane lipoprotein controlacceptablePaired DcrB pH structures are useful controls but should not overweight one protein family in broader claims.
13EE:Apaired membrane lipoprotein controlacceptablePaired DcrB pH structures are useful controls but should not overweight one protein family in broader claims.
13FT:Aclean lipid-transfer domainacceptableNo major biological caveat beyond single-run computational-benchmark scope.
11BC:Ccomplex-derived coverage probecoverage caveatOnly 63 aligned reference residues were scored, so lDDT supports operational/scoring QA but not a full-chain biological-quality claim.
12OY:Amembrane complex stress casecontext caveatMembrane/complex cryo-EM context and 3.6 A resolution make this a stress case; use for viability, not biological generality.
9H8N:Along membrane transport stress caseacceptableLong membrane transporter cryo-EM target; strong for memory/runtime stress, cautious for general quality interpretation.
9K9X:Along enzyme contextacceptableNo major biological caveat beyond single-run computational-benchmark scope.
9K9Y:Along enzyme ligand contextacceptableLigand-bound context is useful, but this benchmark does not evaluate ligand placement or affinity.

Reviewer Questions

  1. Are the paired DcrB structures acceptable as controls, or do they overweight one family?
  2. Should 11BC:C remain in aggregate quality tables, or only in scoring-QA discussion?
  3. Is 12OY:A acceptable as a membrane/complex stress case despite 3.6 A resolution?
  4. Can 9H8N:A be described as a transporter stress target without implying transporter-general performance?
  5. Should 9K9Y:A mention ligand context only as provenance, with no ligand-quality interpretation?

Artifacts

Source document: docs/36_phase1a_biological_review.md. External biological review is still pending before biological generality claims.