proteinmpnn

ProteinMPNN Sequence Design

Prerequisites

Requirement	Minimum	Recommended
Python	3.8+	3.10
CUDA	11.0+	11.7+
GPU VRAM	8GB	16GB (T4)
RAM	8GB	16GB

How to run

First time? See Getting started to set up Modal and biomodals.

Option 1: Local installation (recommended)

git clone https://github.com/dauparas/ProteinMPNN.git
cd ProteinMPNN

python protein_mpnn_run.py \
  --pdb_path backbone.pdb \
  --out_folder output/ \
  --num_seq_per_target 16 \
  --sampling_temp "0.1"

GPU: T4 (16GB) sufficient | Time: ~50-100 sequences/minute

Option 2: Modal (via LigandMPNN wrapper)

cd biomodals
# modal_ligandmpnn.py takes --input-pdb and forwards run.py args via --params-str
modal run modal_ligandmpnn.py \
  --input-pdb backbone.pdb \
  --params-str "--model_type protein_mpnn --number_of_batches 16 --temperature 0.1"

GPU (Modal): A10G default | Timeout: 900s default

Note: LigandMPNN includes ProteinMPNN functionality (select with --model_type protein_mpnn).

Config Schema

Core Parameters

Parameter	Default	Range	Description
--pdb_path	required	path	Single PDB input
--pdb_path_chains	all	A,B	Chains to design (comma-sep)
--out_folder	required	path	Output directory
--num_seq_per_target	1	1-1000	Sequences per structure
--sampling_temp	"0.1"	"0.0001-1.0"	Temperature (string!)
--seed	0	int	Random seed
--batch_size	1	1-32	Batch size

Temperature Guide

0.1  -> Low diversity, high recovery (production)
0.2  -> Moderate diversity (default)
0.3  -> Higher diversity (exploration)
0.5+ -> Very diverse, lower quality

IMPORTANT: Temperature must be passed as a string, not float.

Common mistakes

Temperature Parameter

✅ Correct:

--sampling_temp "0.1"    # String with quotes

❌ Wrong:

--sampling_temp 0.1      # Float without quotes - may cause errors
--sampling_temp 0.1,0.2  # Multiple temps need proper format

Fixed Positions JSONL

✅ Correct:

{"A": [1, 2, 3, 10, 11], "B": [5, 6]}

❌ Wrong:

{"A": "1,2,3,10,11"}     # String instead of list
{A: [1, 2, 3]}           # Missing quotes on key
{"A": [1,2,3,]}          # Trailing comma