A New Best Structure Prediction Protocol

A New Best Structure Prediction Protocol

On the comprehensive FoldBench benchmark, IntFold’s performance is comparable to AlphaFold 3 and significantly exceeds other contemporary models (Boltz-1, 2, Chai-1, HelixFold 3 and Protenix) across a diverse range of biomolecular interaction tasks.

Use it on Tamarind Bio today:

In antibody-antigen (Ab-Ag) complexes, commercially useable alternative lagged significantly behind AlphaFold3, until now.


Performance Results

IntFold achieves performance comparable to AlphaFold 3 on the comprehensive FoldBench benchmark:


Protein monomers: 0.88 LDDT score (matching AlphaFold 3)

Protein-protein interactions: 72.9% success rate (matching AlphaFold 3)

Significantly outperforms other contemporary models like Boltz-1/2, Chai-1, HelixFold 3, and Protenix


Antibody-Antigen Complexes

A particularly challenging area where IntFold shows strong improvement:

Base model: 37.6% success rate

Enhanced IntFold+: 43.2% success rate (approaching AlphaFold 3's 47.9%)


Protein-Ligand Interactions

Base model: 58.5% success rate

IntFold+: 61.8% success rate (vs AlphaFold 3's 64.9%)

Structural Constraints: Dramatic improvements when incorporating known binding sites:

PoseBusters dataset: 79.5% → 89.7% success rate

Antibody-antigen interfaces: 37.6% → 69.0% success rate

Binding Affinity Prediction: Outperformed existing methods on DAVIS and BindingDB benchmarks

Technical Advances

Custom FlashAttentionPairBias kernel: Faster and more memory-efficient than standard industry implementations

Model-agnostic ranking method: Training-free approach that improves success rates by ~3% through structural similarity consensus

Practical Impact

IntFold demonstrates the potential for controllable foundation models in drug discovery, successfully addressing limitations of general-purpose models by enabling:

  • Prediction of functionally critical conformational states

  • Integration of prior structural knowledge

  • Accurate binding affinity estimation for virtual screening