v0.1 · Manuscript in preparation

A physics-informed layer for protein–protein docking.

ProteinDock is a lightweight Rosetta layer that lifts top-1 docking reliability across general protein–protein and antibody–antigen benchmarks — with a pre-relax step, a single fa_elec × 1.5 reweight, and interface-aware refinement. No new score function. No new sampler.

Top-1 success rate across three benchmarks.

§ 01 — Readout
DB5.5 · General PPI
80.2%
▲ +32.8 pts
vs vanilla Rosetta 47.4%
SAbDab-v3 · Antibody–Antigen
74.1%
▲ +8.6 pts
vs vanilla Rosetta 65.5%
novel-50 · Post-AF3 Ab–Ag
100%
▲ +2.0 pts
vs vanilla Rosetta 98.0%

Two modes. Same recipe.

§ 02 — Modes
Mode 1 — Docking layer

Refines physics-based docking on chain inputs.

Drop in as a layer over Rosetta's docking protocol. FastRelax each monomer, run local rigid-body sampling with an fa_elec × 1.5-reweighted REF2015, refine the interface, select top-1.

  • Inputs 2 chain PDBs
  • Sampler Rosetta local dock
  • Score REF2015 · fa_elec × 1.5
  • Selection Top-1 by I_sc
Mode 2 — Scoring layer

Reranks foundation-model predictions.

Take pose candidates from AlphaFold3 and Boltz-2, rescore by Rosetta interface energy under the same electrostatic reweight, and arbitrate across predictors. No re-sampling; a truncated ProteinDock scoring pass.

  • Inputs AF3 · Boltz-2 poses
  • Sampler none (score-only)
  • Metric dG_interface
  • Selection Cross-predictor argmin

The recipe — three deliberate changes.

§ 03 — Method
01
Pre-relax each monomer.
Independent FastRelax on each chain before docking. Removes internal strain that would otherwise force docking search away from the true basin.
02
Local docking under a reweighted score.
Rosetta's local dock with fa_elec × 1.5. The 50 % boost to the electrostatic term recovers the polar, charge-driven interfaces that vanilla REF2015 systematically under-selects.
03
Interface refinement and top-1 selection.
All-atom side-chain refinement across the interface, then top-1 by interface energy (I_sc). No ensembles, no oracles, no reranker post-hoc.

Cite

§ 04 — Reference
Rajagopal, G., Spina, S. C., Bailey Jr., J. S., & Kimmel, B. R. (2026). ProteinDock: A physics-informed layer to improve protein–protein docking reliability. Manuscript in preparation.