CG2AT2: an Enhanced Fragment-Based Approach for Serial Multi-scale Molecular Dynamics Simulations

Coarse-grained molecular dynamics provides a means for simulating the assembly and interactions of macromolecular complexes at a reduced level of representation, thereby allowing both longer timescale and larger sized simulations. Here, we describe an enhanced fragment-based protocol for converting macromolecular complexes from coarse-grained to atomistic resolution, for further refinement and analysis. While the focus is upon systems that comprise an integral membrane protein embedded in a phospholipid bilayer, the technique is also suitable for membrane-anchored and soluble protein/nucleotide complexes. Overall, this provides a method for generating an accurate and well-equilibrated atomic-level description of a macromolecular complex. The approach is evaluated using a diverse test set of 11 system configurations of varying size and complexity. Simulations are assessed in terms of protein stereochemistry, conformational drift, lipid/protein interactions, and lipid dynamics.

Automated summary

Coarse-grained molecular dynamics offers a way to simulate macromolecular complexes at a reduced level of representation, allowing for longer timescales and larger simulations. This study presents an enhanced fragment-based protocol for converting such complexes to atomistic resolution, suitable for a variety of systems including integral membrane proteins. Evaluation of the approach on 11 system configurations shows promising results in accurately describing and balancing atomic-level descriptions of macromolecular complexes.