FoldBench

ESMFold2 matches AlphaFold 3 performance with open, LLM-inspired architecture for molecular structure prediction

Biohub and EvolutionaryScale released ESMFold2, a 6.2-billion-parameter open-weights model for predicting the 3D shapes of proteins, DNA, RNA, and small molecules by treating molecular sequences as language. Unlike AlphaFold 3, ESMFold2 can operate without multiple sequence alignments (MSAs) by using a transformer-based embedding model (ESMC) trained on 2.8 billion sequences, outperforming Chai-1 in MSA-free settings and matching AlphaFold 3 when MSAs are provided. The model weights are freely available on HuggingFace and via API through Biohub, making frontier-level structural biology accessible without proprietary infrastructure. The release is significant for drug discovery involving novel or synthetic molecules where MSA databases may be sparse.