OpenAWSEM

OpenAWSEM implements a coarse-grained molecular dynamics force field for proteins within the OpenMM framework to enable efficient GPU-accelerated simulation and coupling with Open3SPN2 for protein–DNA modeling.

Key Features:

• GPU Acceleration: Leverages GPU execution in OpenMM to accelerate protein and protein–DNA simulations with reported >100-fold speedup relative to CPU-based LAMMPS implementations.
• OpenMM Custom Forces Framework: Uses OpenMM’s Custom Forces framework to express and modify forcefield potentials flexibly.
• AWSEM Coarse-Grained Potentials: Implements the Accelerated Weighted Structure-based Energy Model (AWSEM) coarse-grained potentials for proteins.
• Integration with Open3SPN2: Couples with Open3SPN2 coarse-grained DNA model to simulate protein–DNA interactions and binding landscapes.
• Membrane-Burial Potential: Implements a novel potential that models changes in effective interactions when a protein becomes partially buried in a membrane.
• Multi-Body Disulfide Bonding Term: Implements an advanced multi-body disulfide term to prevent unphysical cysteine clustering and to reproduce Anfinsen-type disulfide formation behavior.

Scientific Applications:

• Large biomolecular complexes: Simulates conformational dynamics of large assemblies, including ribosomes.
• CRISPR-Cas9 systems: Models conformational and binding behavior of CRISPR-Cas9 with DNA.
• Transcription factors and DNA-wrangling proteins: Studies interactions of transcription factors and SMC-Kleisins with DNA.
• Protein folding and structure prediction: Investigates protein folding dynamics and disulfide-bonded protein behavior consistent with classical Anfinsen experiments.

Methodology:

Coarse-grained molecular modeling implemented in OpenMM using GPU acceleration and OpenMM Custom Forces; integration of AWSEM for proteins and Open3SPN2 for DNA; explicit novel membrane-burial potential and multi-body disulfide bonding term are implemented, with reported >100-fold speedup versus CPU LAMMPS.