Nature: "Accurate structure prediction of biomolecular interactions with AlphaFold 3" (2024)
Extension: Proteins + DNA + RNA + small molecules (ligands) + covalents
Application: Drug design — predict how a drug fits into the protein
Access: alphafoldserver.com (restricted to non-commercial research)
Protein Language Models (PLMs)
ESM-1/2 (Meta AI)
ESM-1: arXiv:2019.08 — Transformer on amino acid sequences
ESM-2: arXiv:2202.03460 — 15B parameters; largest PLM; structure emergent from sequence alone
ESMFold: Structure prediction without MSA (faster than AlphaFold 2)
ESM-3 (EvolutionaryScale, 2024)
arXiv: 2024.06 (Science, 2024)
Biological multimodal: Sequence + structure + function in a single model
Parameters: 98B
Result: Generated functional fluorescent proteins without evolutionary precedent
Highlight: First evidence of AI creating genuinely new proteins
Protein Diffusion — Generative Design
RFdiffusion (Baker Lab, UW, 2023)
Nature: "De novo protein design by inversion of RoseTTAFold structure prediction" (2023)
Mechanism: Diffusion model over protein structures; protein design from scratch
Result: Functional proteins with entirely novel scaffolds
ProteinMPNN (Baker Lab, 2022)
Science: 2022
Function: Given a backbone, design a sequence that folds into that structure
Complementary to RFdiffusion: RFdiffusion makes the backbone; ProteinMPNN makes the sequence
Evolutionary-Based Biology
Evo 1 (Arc Institute, 2024)
arXiv: 2402.xxxxx
Architecture: StripedHyena (hybrid SSM + MHA)
Data: 2.7M whole prokaryotic genomes
Window: 131K tokens (nucleotides)
Result: Predicts the effect of mutations; generates functional biological sequences
Evo 2 (Arc Institute, 2026)
Nature: "Genome modelling and design across all domains of life with Evo 2" (natureza.comarticless41586-026-10176-5)
Data: 9T base pairs of DNA; 100,000+ species; all domains of life (Bacteria, Archaea, Eucaryota)
Parameters: 40B
Window: 1M nucleotides — spans complete genomes
Highlight: First model to model and generate genomic sequences across all domains of life; generated functional whole-chromosome DNA; predicts splicing disease with clinical accuracy
Genomics and Epigenomics
AlphaGenome (Google DeepMind, 2025)
Focus: Predicts genetic regulation (gene expression, splicing, enhancers) from DNA sequence
Input: 1M base pairs of DNA sequence
Output: Chromatin accessibility patterns, expression, splicing per tissue
Impact: Identify genetic variants causal of diseases
Enformer (DeepMind, 2021)
Nature Methods: 2021
Focus: Gene expression prediction from DNA sequence
Architecture: Transformer with long-range attention
Drug Discovery
AlphaFold + Drug Design Pipeline
AlphaFold 3 predicts the target structure
ProteinMPNN designs the inhibitor
Virtual docking selects candidates
Experimental synthesis and testing
Isomorphic Labs (DeepMind spinout)
Exclusive focus on AI-driven drug discovery
Partnerships with Eli Lilly, AstraZeneca (2024)
AlphaFold pipelines applied to therapeutic targets
AbSci / Xaira Therapeutics
Antibody design with generative AI
Clinical Bioinformatics
Google MedPaLM 2
Medical: Fine-tuning of PaLM 2 for medical questions