ESMFold2-Fast

Model overview

Synthyra/ESMFold2-Fast packages the biohub/ESMFold2-Fast checkpoint with the FastPLMs runtime for Hugging Face Transformers. It accepts raw amino-acid sequences or typed molecular-complex specifications; low-level forward accepts prepared feature tensors.

The repository uses the standard Transformers loading interface with trust_remote_code=True. See Technical details for each registered class and whether its weights come from the checkpoint.

The sequence- and token-classification classes reuse the pretrained backbone, but their task heads are newly initialized. Fine-tune those heads before interpreting their logits as predictions.

Install and platform requirements

Install the direct dependencies published with this model:

python -m pip install -r \
  "https://huggingface.co/Synthyra/ESMFold2-Fast/resolve/main/requirements.txt"

The FastPLMs implementation itself is embedded in the model repository. Transformers loads it through trust_remote_code=True.

This model requires Python 3.11-3.14, PyTorch 2.13, and Transformers 5.13.

The artifact requirements include the structure dependencies.

The release contract requires a CUDA device. The current validated target is the exact NVIDIA GH200 on Linux aarch64. Linux x86-64, CPU-only, Windows, and macOS structure runs are not release evidence.

The Hub quick start needs network access for the first download. For an air-gapped run, build the manifest-pinned local artifact first and use the offline example.

Quick start

from transformers import AutoModel

model_id = "Synthyra/ESMFold2-Fast"
model = AutoModel.from_pretrained(
    model_id,
    trust_remote_code=True,
    attn_implementation="sdpa",
).eval()

For offline validation, replace model_id with the manifest-built dist/hub/ESMFold2-Fast path. Pass local_files_only=True.

Attention backends

The quick start uses sdpa.

Available backends are eager, sdpa, flex_attention. Requesting an unavailable backend raises instead of silently changing implementation.

output_attentions=True can use the documented one-call eager fallback to materialize attention tensors. The configured backend does not change.

Downstream prediction

The sequence and token prediction AutoClasses use the checkpoint backbone and create a new, untrained classifier. Sequence labels have shape (b,). Residue labels have shape (b, l) and use -100 outside biological positions. The folding trunk is skipped. The classifier uses the checkpoint's learned pLM state mixture and projection, followed by one trainable transformer probe.

import torch
from transformers import (
    AutoModelForSequenceClassification,
    AutoModelForTokenClassification,
)

model_id = "Synthyra/ESMFold2-Fast"
sequence_model = AutoModelForSequenceClassification.from_pretrained(
    model_id, num_labels=2, trust_remote_code=True
).eval()
token_model = AutoModelForTokenClassification.from_pretrained(
    model_id, num_labels=3, trust_remote_code=True
).eval()
sequences = ["MSTNPKPQRKTKRNT", "MKTIIALSYIFCLVFA"]
batch = sequence_model.prepare_classifier_inputs(sequences)
biological = batch["attention_mask"].bool()

sequence_labels = torch.zeros(len(sequences), dtype=torch.long)
token_labels = torch.full_like(batch["input_ids"], -100)
token_labels[biological] = 0

with torch.inference_mode():
    sequence_output = sequence_model(**batch, labels=sequence_labels)
    token_output = token_model(**batch, labels=token_labels)
print(sequence_output.logits.shape)  # (b, 2)
print(token_output.logits.shape)     # (b, l, 3)

PEFT fine-tuning

Install the training dependencies. Then attach LoRA to the loaded checkpoint:

python -m pip install "datasets>=4.8,=0.19,<0.20"

from peft import LoraConfig, TaskType, get_peft_model

peft_model = get_peft_model(
    sequence_model,
    LoraConfig(
        task_type=TaskType.SEQ_CLS,
        r=8,
        lora_alpha=16,
        target_modules="all-linear",
        modules_to_save=["classifier"],
    ),
)

This checkpoint advertises a classification head. Save the separately trained classifier with the adapter. All FastPLMs checkpoints follow the Transformers PreTrainedModel contract and can use PEFT. The ESM2-specific shipped CLI is an example, not a support boundary. Record the target modules, base revision, data identity, and trainable parameter scope.

Alignment-conditioning contract

This 24-block Fast checkpoint is optimized for single-sequence inference. It was trained without MSA conditioning. It rejects ProteinInput.msa and low-level MSA-derived features. Typed multichain and multimolecule inputs remain supported when every protein chain uses msa=None. Use the full ESMFold2 checkpoint for MSA-conditioned inference. This follows the official Biohub architecture description in Appendix A.2.1.

Protein folding

The single-protein helper returns typed structure and confidence outputs:

result = model.fold_protein(
    "MSTNPKPQRKTKRNT",
    num_loops=1,
    num_sampling_steps=200,
    num_diffusion_samples=1,
    seed=7,
)
pdb_text = model.result_to_pdb(result)
cif_text = model.result_to_cif(result)
print(result.ptm, result.plddt.mean().item())

No target structure is required. For complexes, construct the input from the types exposed by the loaded artifact:

types = model.input_types
complex_input = types.StructurePredictionInput(
    sequences=[
        types.ProteinInput(id="A", sequence="MSTNPKPQRKTKRNT"),
        types.ProteinInput(id="B", sequence="MKTIIALSYIFCLVFA"),
        types.DNAInput(id="C", sequence="ATGC"),
        types.LigandInput(id="L", smiles="O"),
    ]
)
complex_result = model.fold(
    complex_input,
    num_loops=1,
    num_sampling_steps=200,
    seed=7,
)
print(complex_result.ptm, complex_result.plddt.mean().item())

The typed interface also supports RNA, modifications, and covalent