A Scalable and Quantum-Accurate Foundation Model for Biomolecular Force Field via Linearly Tensorized Quadrangle Attention

TL;DR

LiTEN introduces a scalable, quantum-accurate neural network with tensorized attention for biomolecular simulations, outperforming existing models in accuracy and speed, and enabling comprehensive downstream tasks.

Contribution

The paper presents LiTEN, a novel equivariant neural network with tensorized quadrangle attention, achieving high accuracy and efficiency in biomolecular force field modeling, and introduces LiTEN-FF for broad chemical generalization.

Findings

LiTEN outperforms MACE, NequIP, and EquiFormer on benchmark datasets.

LiTEN-FF enables QM-level conformer searches and geometry optimization.

LiTEN offers 10x faster inference than MACE-OFF for large biomolecules.

Abstract

Accurate atomistic biomolecular simulations are vital for disease mechanism understanding, drug discovery, and biomaterial design, but existing simulation methods exhibit significant limitations. Classical force fields are efficient but lack accuracy for transition states and fine conformational details critical in many chemical and biological processes. Quantum Mechanics (QM) methods are highly accurate but computationally infeasible for large-scale or long-time simulations. AI-based force fields (AIFFs) aim to achieve QM-level accuracy with efficiency but struggle to balance many-body modeling complexity, accuracy, and speed, often constrained by limited training data and insufficient validation for generalizability. To overcome these challenges, we introduce LiTEN, a novel equivariant neural network with Tensorized Quadrangle Attention (TQA). TQA efficiently models three- and four-body interactions with linear complexity by reparameterizing high-order tensor features via vector operations, avoiding costly spherical harmonics. Building on LiTEN, LiTEN-FF is a robust AIFF foundation model, pre-trained on the extensive nablaDFT dataset for broad chemical generalization and fine-tuned on SPICE for accurate solvated system simulations. LiTEN achieves state-of-the-art (SOTA) performance across most evaluation subsets of rMD17, MD22, and Chignolin, outperforming leading models such as MACE, NequIP, and EquiFormer. LiTEN-FF enables the most comprehensive suite of downstream biomolecular modeling tasks to date, including QM-level conformer searches, geometry optimization, and free energy surface construction, while offering 10x faster inference than MACE-OFF for large biomolecules (~1000 atoms). In summary, we present a physically grounded, highly efficient framework that advances complex biomolecular modeling, providing a versatile foundation for drug discovery and related applications.