Skip to content

rinikerlab/rest2_ampmm

BranchesTags

Repository files navigation

REST2-AMP/MM

Logo

Overview

REST2-AMP/MM provides the code, parameters, and pretrained weights for the
AMPv3-BMS25 multiscale neural network potential, together with full support for
AMP/MM and REST2-AMP/MM simulation workflows.

This repository enables:

  • Multiscale neural network simulations of proteins, peptides, and small organic molecules
  • AMP/MM equilibration and production MD runs
  • REST2-AMP/MM enhanced sampling simulations

Installation

This project is designed to be used with conda/mamba.

1. Create environment

conda env create -f environment.yaml
conda activate rest2_ampmm

2. Install the package

pip install -e .

Model Description

AMP-BMS is a multiscale neural network potential trained on QM/MM data with electrostatic embedding for simulations of biomolecules in the condensed phase.

The model:

  • is based on the AMP architecture
  • is trained on high-level QM/MM reference data
  • enables efficient and accurate condensed-phase simulations

Related Work

Running Simulations

Simulations are typically carried out through the following stages:

NVT → NPT → production or REST2

Each stage consists of:

  1. Generating a config.yaml
  2. Submitting it to the scheduler

General Setup

Before running any stage, generate input files using the corresponding script.

The molecule name determines the QM region and charge and must be consistent across all steps.

Placeholders:

  • <PDB_NAME> — system name (e.g. ALA)
  • <QM_RESIDUES> — QM region (e.g. ACE ALA NME)
  • HOH — MM region (water)
  • <CHARGE> — QM charge (e.g. 0 for neutral systems)

Ensure consistency across all scripts:

nvt.py, npt.py, production.py, rest2.py

Stage Commands

NVT

python input_generation_scripts_examples/nvt.py \
  --molecule <PDB_NAME> \
  --qm_zone <QM_RESIDUES> \
  --mm_zone HOH \
  --mol_charge <CHARGE> \
  --output nvt

NPT

python input_generation_scripts_examples/npt.py \
  --molecule <PDB_NAME> \
  --qm_zone <QM_RESIDUES> \
  --mm_zone HOH \
  --mol_charge <CHARGE> \
  --input nvt \
  --output npt

Production

python input_generation_scripts_examples/production.py \
  --molecule <PDB_NAME> \
  --qm_zone <QM_RESIDUES> \
  --mm_zone HOH \
  --mol_charge <CHARGE> \
  --restart_velocities  # if needed \
  --input npt \
  --output production_0000

REST2

Define:

  • number of replicas
  • scaling range

Scaling distributions are configurable in:

src/helper_functions.py

python input_generation_scripts_examples/rest2.py \
  --molecule <PDB_NAME> \
  --qm_zone <QM_RESIDUES> \
  --mm_zone HOH \
  --mol_charge <CHARGE> \
  --restart_velocities  # if needed \
  --input npt \
  --output rest2_0000_0000

Output Structure

Each stage creates:

amp_simulation/<PDB_NAME>/<STAGE>/

containing:

  • config.yaml (editable)

Submitting Jobs

sbatch --wrap="rest2-ampmm amp_simulation/<PDB_NAME>/<STAGE>/config.yaml"
  • <STAGE>: nvt, npt, production, rest2

Ensure SLURM resources are compatible with your simulation setup.

Automated SLURM Submission

Example script:

submission_scripts_examples/submit_SLURM_simulations.sh

This script automates:

  • input generation
  • job submission

For production and REST2, it submits a chain of dependent jobs:

  • one job per trajectory segment
  • sequential execution (afterok)
  • automatic restart from previous segment

Usage

bash submission_scripts_examples/submit_SLURM_simulations.sh <MOLECULE> <STAGE> [N_REPS]
  • <MOLECULE>:
    ALA, CYC2, CYC2t, P13n, P13e, TRP, TRPu, CLN, CLNunf, CHICF, CHIC
  • <STAGE>: nvt, npt, production, rest2
  • [N_REPS]: number of independent replicates (default = 1)

Note
N_REPS refers to independent simulations (replicates),
not to replicas used internally in REST2.

Examples

# NVT equilibration (single job)
bash submission_scripts_examples/submit_SLURM_simulations.sh ALA nvt

# NPT equilibration (single job, continues from NVT)
bash submission_scripts_examples/submit_SLURM_simulations.sh ALA npt

# Production (chain of jobs, 1 independent replicate)
bash submission_scripts_examples/submit_SLURM_simulations.sh ALA production 1

# REST2 (MPI + GPU, 1 independent replicate)
bash submission_scripts_examples/submit_SLURM_simulations.sh ALA rest2 1

Notes

  • NVT / NPT

    • single SLURM job

  • Production / REST2

    • segmented trajectories
    • sequential job dependencies
    • support multiple independent replicates

  • Logs are written to:

logs/

Repository Structure

input_generation_script_examples/

Contains examples for generating YAML configuration files for:

  • NVT equilibration (nvt.py)
  • NPT equilibration (npt.py)
  • Production MD (production.py)
  • REST2-AMP/MM simulations (rest2.py)

submission_script_examples/

Contains example scripts for HPC submission of chained REST2-AMP/MM and production MD AMP/MM jobs, where:

  • MD simulations are split into chunks
  • Each chunk is submitted as a dependency of the previous job
  • The jobs are run on a cluster with SLURM

analysis/

Contains analyses related to the REST2-AMP/MM publication, including:

  • NOE violation calculations (cyclic_peptides.py, trp_noe.py, cln_noe_folded.py, cln_noe_unfolded.py)
  • Roundtrips and exchange analysis (roundtrips_exchange_acceptance.py)
  • C-alpha RMSD calculations (trp_structural_analysis.py, cln_chignolin.py)
  • RMSD of interatomic distances (cln_chignolin.py)
  • Ramachandran analysis (alanine_polyproline.py, cyclic_peptides.py)

data/

Contains:

  • Starting structures of all systems in PDB format related to the REST2-AMP/MM publication (starting_structures)
  • Examples of config.yaml files used for NVT equilibration, NPT equilibration, production MD, and REST2-AMP/MM runs (example_input_configs)

related to the REST2-AMP/MM publication

configs/deafult/

Contains:

  • Default JSON configurations of OpenMM/MDTraj StateDataReporter (default_csv_parameters.json) and HDF5 reporter (default_hdf5_parameters.json)
  • Default JSON configurations of OpenMM force field XML files to be used with TIP4P-FB (ff_default_tip4pfb.json) and TIP3P (ff_default.json) water models

resources/

Contains:

  • AMPv3 YAML parameter files to be used with TIP4P-FB (PARAMETERS_MIN_LRv2_tip4pfb.yaml) and TIP3P water models (PARAMETERS_MIN_LRv2.yaml)
  • AMPv3-BMS25 models weights (MIN_LRv2_state_dict)

References

If you use this code, please cite our papers:


@article{REST2_AMP,
    title = {Quantum-Accurate Enhanced Sampling and Mini-Protein Folding through Replica Exchange for Multiscale Neural Network Potentials},
    author = {Solazzo, Riccardo and Gordiy, Igor and Riniker, Sereina},
    journal = {ChemRxiv},
    year = {2026}
    doi = {\url{https://doi.org/10.26434/chemrxiv.15001723/v1}},

}

@article{AMP_BMS,
    title = {{AMP}-{BMS}/{MM}: A Multiscale Neural Network Potential for the Fast and Accurate Simulation of Protein Dynamics and Enzymatic Reactions},
    author = {Th{\"u}rlemann, Moritz and Pultar, Felix and Gordiy, Igor and Ruijsenaars, Enrico and Riniker, Sereina},
    journal = {ChemRxiv},
    year = {2026}
    doi = {\url{https://chemrxiv.org/doi/10.26434/chemrxiv-2026-kx9w0}},
}

@article{BMS25,
title = {Biomolecular Simulation ({BMS}) Dataset to Train Multiscale Neural Network Potentials},
author = {Th{\"u}rlemann, Moritz and Pultar, Felix and Gordiy, Igor and Riniker, Sereina},
journal = {ChemRxiv},
year = {2025},
doi = {\url{https://chemrxiv.org/doi/10.26434/chemrxiv-2025-xzp6k}},
}

@article{AMPv2,
title = {Neural Network Potential with Multiresolution Approach Enables Accurate Prediction of Reaction Free Energies in Solution},
author = {Pultar, Felix and Th{\"u}rlemann, Moritz and Gordiy, Igor and Doloszeski, Eva and Riniker, Sereina},
journal = {J. Am. Chem. Soc.},
volume = {147},
pages = {6835--6856},
year = {2025},
doi={https://doi.org/10.1021/jacs.4c17015}
}


@article{AMP,
  title = {Anisotropic Message Passing: Graph Neural Networks with Directional and Long-Range Interactions},
  author = {Th{\"u}rlemann, Moritz and Riniker, Sereina},
  journal = {The Eleventh International Conference on Learning Representations},
  year = {2023},
  doi = {\url{https://openreview.net/forum?id=socffUzSIlx}},
  note = {(accessed 2025-12-13)},
}

Contributors

  • Igor Gordiy
  • Riccardo Solazzo
  • Moritz Thürlemann
  • Felix Pultar
  • Enrico Ruijsenaars

Acknowledgements

The authors thanks Antonia Kuhn and Stefan Chrin for code review and Francisco J. Enguita for the logo design.

License

The REST2-AMP/MM code is published and distributed under the MIT License.

About

No description, website, or topics provided.

Resources

Readme

License

MIT license
Activity
Custom properties

Stars

5 stars

Watchers

0 watching

Forks

1 fork
Report repository

Releases

No releases published

Packages

 
 
 

Contributors 1

Languages