meiler lab / vanderbilt computational structural biology
a protein benchmark
that fails closed
may 2025 - present / remote from seattle / computational pipeline development + analysis
The BM5.5 project asks how Boltz-2 predictions change under matched physics-based relaxation, and whether those changes help complex geometry, interface quality, or only local stereochemistry. The hard part is not generating another figure. It is making every comparison traceable to the exact model, structure, protocol, score, and completion receipt that produced it.
bm5.5 / end-to-end workflow
Every lane is isolated until identity, method, and denominator checks pass. Archived Boltz-1 work remains available as a historical baseline but does not enter the new Boltz-2 claims.
A structure count is not a completion claim. The manuscript gate requires the exact Rosetta output set, all three postscore families, independent audits, and reproducible tables and figures.
benchmark and identity freeze
Each BM5.5 target, prediction lane, sample, relaxation method, replicate, and output path receives a collision-proof identity. Source hashes, method identifiers, environment captures, and expected denominators are fixed before analysis.
Boltz-2 structure prediction
Boltz 2.2.1 runs with the Boltz-2 model, five diffusion samples, ten recycling steps, and 200 sampling steps. Two independently seeded lanes yield 1,285 models each across the 257 targets.
matched AMBER relaxation
Every raw prediction is paired with the captured paper-method AlphaFold 2.3.2 AmberRelaxation implementation. The executable provenance, rather than remembered method wording, defines the canonical lane.
multi-protocol Rosetta relaxation
Six Rosetta protocol families and their replicate matrix are applied without pooling partial lanes. The complete planned release contains exactly 154,200 structure identities.
three-axis structural scoring
TM-score measures global fold similarity, DockQ and its components resolve interface quality, and MolProbity measures local stereochemistry. Each completed structure must produce all three score rows.
stratification and manuscript promotion
Only complete, validated tables feed comparisons by complex category, size, difficulty, prediction lane, and relaxation method. Main-text figures carry the shortest defensible result; exhaustive protocol detail remains in the supplement.
current verified state
The page reports fixed, audited milestones. It does not turn an active compute lane into a scientific conclusion.
raw Boltz-2 complete
Both prediction lanes are complete at 1,285 structures each, for 2,570 unique raw model identities. TM-score, DockQ, and MolProbity tables are complete at 7,710 metric rows.
complete / 2,570 structures + 7,710 metricspaper-method AMBER complete
The matched relaxation lane is complete at 2,570 outputs, one for every raw Boltz-2 identity, with its own 7,710-row score release and immutable provenance.
complete / exact one-to-one pairingRosetta + postscore active
The canonical matrix is still progressing toward 154,200 Rosetta outputs and 462,600 corresponding metric rows. Partial counts remain operational status, not evidence for rankings.
active / final denominator not yet sealedfinal comparisons withheld
No protocol winner or integrated Boltz-2 conclusion is promoted until the exact output and postscore receipts pass, followed by table, figure, reference, and manuscript checks.
fail closed / claims pendingThe June lab review emphasized that outliers cannot be silently rerun or discarded, interface quality must be decomposed, and results must be stratified by protein class and size. The current pipeline encodes those methodological requirements directly instead of repairing them after the figures are drawn.
The earlier program generated more than 6,800 structures from AlphaFold 2.3.2 and Boltz-1 v0.4.1 across the same 257-complex BM5.5 benchmark. It evaluated six Rosetta 3.15 FastRelax protocols with five replicates each, followed by MolProbity and PoseBusters checks including clashscore, Ramachandran outliers, rotamer quality, Cβ deviations, bond lengths, bond angles, and steric clashes. Those results remain a documented baseline, but they are not presented as current Boltz-2 evidence.
planned analysis / the questions behind the plots
parallel work / alphavirus stabilization
The benchmark grew out of a broader Meiler Lab role supporting computational design in an ARPA-H-funded alphavirus vaccine program.
pipeline integration
ThermoMPNN, ESM, ProteinMPNN, MIF-ST, structure prediction, physics-based relaxation, and structural validation are connected into a reproducible path so the design team can move from a candidate sequence to a reviewable structure set for VEEV and MAYV envelope glycoproteins.
design-team support
The infrastructure is built for iteration: configurable batch submission, restart-safe outputs, explicit environments, and analysis tables that let experimental collaborators compare candidates without reconstructing the compute history.
I built and maintain the prediction, relaxation, scoring, provenance, and figure-generation workflows; coordinate long-running HPC and workstation lanes; audit denominators and identities; and draft the first-author BM5.5 analysis under guidance from the Meiler Lab team.
papers + open infrastructure
Benchmarking Boltz-2 Prediction and AMBER Relaxation on BM5.5 Protein Complexes
First author. Prediction, matched relaxation, interface scoring, and stratified analysis.
alphavirus stabilization for vaccine design
Contributing author. Computational pipeline for the ARPA-H program.
VICB Summer Symposium talk
Alphavirus vaccine development through computational stabilization, Nashville.
watch the talk ↗Protein_Data_Analysis
Structural scoring, MolProbity validation, geometry checks, comparative statistics, and figure generation.
Protein_Relax_Pipeline
Configurable Rosetta and AMBER relaxation workflows with HPC batch submission and restart-safe outputs.
Protein_Ideal
The earlier BM5.5 release and analysis scaffold. Its Boltz-1-era results remain an archived baseline rather than being relabeled as Boltz-2.