OpenAWSEM with Open3SPN2: A fast, flexible, and accessible framework for large-scale coarse-grained biomolecular...

Area of Science:

• Computational Biology
• Molecular Biophysics
• Biochemistry

Background:

• Coarse-grained models are essential for simulating large biomolecular systems.
• Existing models like AWSEM and 3SPN2 offer chemical accuracy but lack efficient computational performance for large-scale simulations.
• The OpenMM framework provides a flexible platform for developing and optimizing molecular dynamics force fields.

Purpose of the Study:

• To introduce OpenAWSEM and Open3SPN2, new implementations of protein and DNA coarse-grained models within the OpenMM framework.
• To leverage GPU acceleration for significant speedups in molecular dynamics simulations.
• To develop and implement novel potentials for enhanced protein folding and protein-DNA binding simulations.

Main Methods:

• Developed cross-compatible OpenAWSEM and Open3SPN2 models using OpenMM's Custom Forces.
• Implemented GPU acceleration for molecular dynamics simulations.
• Devised and integrated new potentials for membrane interactions and multi-body disulfide bonding.
• Modeled protein-DNA binding to assess the accuracy of the combined models.

Main Results:

• Achieved a ~30-fold speedup in protein and protein-DNA simulations using GPU acceleration compared to CPU-based methods.
• Successfully implemented novel potentials to model protein-membrane interactions and prevent unphysical clustering in proteins with multiple disulfide bonds.
• Reproduced Anfinsen's experiments computationally using a multi-body disulfide bonding term.
• Protein-DNA binding simulations yielded landscapes consistent with experimental findings.

Conclusions:

• OpenAWSEM and Open3SPN2 provide efficient and user-friendly tools for molecular biophysics research.
• These models facilitate the simulation of large proteins and protein-DNA systems, bridging the gap between molecular and cellular scales.
• The enhanced capabilities enable deeper understanding of protein folding, structure prediction, and protein-DNA interactions relevant to cellular processes.