RIGOR: Post-Docking Triage for Peptide Binder Discovery
RIGOR-Lite is RAPTOR's in-house deterministic scoring phase. It evaluates docked peptide candidates after DiffDock and before GROMACS molecular dynamics, filtering weak or physically implausible binders before expensive simulation. Unlike generic docking scores, RIGOR evaluates whether a candidate forms a resilient interface, occupies meaningful receptor patches, avoids excessive conformational penalty, and remains sequence-developable.
A proprietary RAPTOR scoring phase that converts docked peptide poses into an explainable advance / review / reject decision before molecular dynamics.
Candidate
binder_001
Final Score
78.4/ 100
Confidence
68.5%0–100 scale
Illustrative values for a single docked candidate.
Pipeline placement
Where RIGOR sits in the pipeline
RIGOR is placed after DiffDock because it requires a receptor-peptide docked pose. It is placed before GROMACS because molecular dynamics is computationally expensive. RIGOR therefore acts as a low-cost gate that prevents poor docked poses from consuming downstream simulation resources.
Motivation
Why RIGOR is needed
Docking scores are not enough
Docking can produce poses that look numerically favorable but lack stable or biologically meaningful receptor-peptide contacts.
MD is expensive
Running molecular dynamics on every generated binder wastes computational resources when many poses are structurally weak.
Peptide binders are flexible
Peptides can appear favorable in a single pose but may pay a large conformational cost or fail to preserve contacts under small perturbations.
Downstream MD cost
IllustrativeRIGOR fills this gap by adding an interpretable post-docking intelligence layer between docking and molecular dynamics.
Hybrid inputs
RIGOR input model
Receptor PDB
- Source:
- PDBFixer — exact file used during DiffDock/SMINA docking
- Purpose:
- Receptor coordinates in the same frame as the docked pose
Docked peptide pose
- Source:
- Selected ranked DiffDock SDF (e.g. rank1_confidence-3.62.sdf)
- Purpose:
- Docked spatial coordinates — preserved exactly, never re-docked
Original peptide sequence
- Source:
- RFdiffusion metadata
- Purpose:
- True peptide identity (not inferred from the SDF)
Exact-coordinate contract
RIGOR must receive the exact receptor file used during DiffDock — not a re-extracted chain — and the exact selected ranked DiffDock SDF (or a coordinate-preserving PDB converted from that same SDF). The peptide sequence always comes from RFdiffusion metadata; RIGOR never infers it from an SDF-derived ligand residue such as LIG, UNL, MOL, or X.
Inside RIGOR-Lite
Component modules
CIRS-lite
Contact Integrity Resilience Scorer
Measures whether receptor-peptide contacts remain stable under small pose perturbations.
- contact persistence
- Jaccard contact retention
- clash penalty
- resilience score
HARP-lite
Hotspot-Aligned Receptor Patch Score
Evaluates whether the peptide contacts coherent and chemically meaningful receptor surface patches.
- contact density
- chemistry match
- patch coherence
- anchor residue fraction
ECHO-lite
Entropic Commitment and Helical Order Proxy
Estimates whether the peptide is too flexible or sufficiently preorganized for binding.
- contact fraction
- flexibility penalty
- internal constraint score
- length/preorganization score
BALM-lite
Bound-state Aware Liability Matrix
Screens peptide sequence liabilities related to developability, synthesis burden, and stability.
- deamidation motifs
- oxidation-prone residues
- hydrophobic clusters
- cysteine complexity
- sequence liability score
FUSE-lite
Fusion and Uncertainty Scoring Engine
Combines all component scores into a single final RIGOR score, confidence value, and decision.
- final score
- confidence
- ADVANCE / REVIEW / REJECT decision
How RIGOR fuses signals
Score formula
RIGOR-Lite Score = 0.40 × CIRS-lite + 0.25 × HARP-lite + 0.20 × ECHO-lite + 0.15 × BALM-lite
The current weights are heuristic starting values and can later be recalibrated using benchmark data or internal experimental results.
From score to action
Decision logic
No-contact rule
If no receptor-peptide interface contacts are detected, the candidate is automatically rejected or flagged as input-error depending on the diagnostic result.
Confidence scale
Confidence is reported on a 0–100 scale. A value of 40 means 40% confidence — the number is already a percent and never multiplied again.
Mock RIGOR report
Visual diagnostic dashboard
Final score
Decision: ADVANCE
Component scores
Weighted contributions
Interface diagnostics
- Atom contacts
- 184
- Residue contacts
- 31
- Receptor contact residues
- 18
- Peptide contact residues
- 13
- Clashes
- 2
- Min Rx–Pep distance
- 2.41 Å
Warnings
- Invalid sequence (X)
- SDF-derived ligand representation
- Coordinate-frame mismatch
- No peptide atoms parsed
Novelty
What makes RIGOR novel inside RAPTOR?
“RIGOR transforms RAPTOR from a pipeline that only integrates external tools into a pipeline with a proprietary decision-making phase.”
RIGOR output
What you get back
ADVANCE
Pose is sent forward into ligand prep and GROMACS MD.
REVIEW
Pose is borderline — you decide whether to continue or stop.
REJECT
Pose is filtered out before expensive simulation.
Score breakdown
- CIRS-lite40%
- HARP-lite25%
- ECHO-lite20%
- BALM-lite15%
Handoff diagram
DiffDock pose
.sdf (exact)
Receptor
.pdb (docking frame)
RFdiffusion
sequence
RIGOR-Lite
Gate decision
advance / review / reject
Component scores
CIRS · HARP · ECHO · BALM
RIGOR receives the exact docked SDF, the exact docking receptor, and the RFdiffusion sequence — and returns a gate decision plus four explainable component scores.
Honest scope
Scientific limitations
RIGOR-Lite is an early-stage triage method, not a direct experimental binding-affinity predictor. It does not replace molecular dynamics or wet-lab validation. It does not fully model induced fit, explicit water networks, metals, glycans, noncanonical residues, or true binding free energy. Its purpose is to provide fast, interpretable prioritization before expensive downstream simulation.
RIGOR turns docking output into a decision
By combining contact resilience, receptor patch relevance, entropy awareness, and sequence developability, RIGOR provides RAPTOR with a novel, explainable, and computationally efficient post-docking triage phase.