SOP-MULTI: A Self-Organized Polymer-Based Coarse-Grained Model for Multidomain and Intrinsically Disordered Proteins...

Area of Science:

• Structural biology
• Computational biophysics
• Protein dynamics

Background:

• Multidomain proteins and intrinsically disordered proteins (IDPs) exist as dynamic ensembles, challenging traditional structural determination.
• Accurate simulation of these proteins requires advanced computational methods capable of handling both folded and disordered regions.

Purpose of the Study:

• To introduce SOP-MULTI, a novel coarse-grained force field for simulating multidomain proteins.
• To enable accurate conformational sampling of proteins containing both folded and intrinsically disordered regions.

Main Methods:

• Development of the SOP-MULTI force field, integrating SOP-SC and SOP-IDP models.
• Introduction of cross-interaction terms for modeling folded and disordered regions within the same polypeptide.
• Simulation of various full-length multidomain proteins including hnRNP A1, TDP-43, and FUS.

Main Results:

• SOP-MULTI successfully generates accurate conformational ensembles for multidomain proteins.
• Back-mapped trajectories from SOP-MULTI faithfully reproduce experimental scattering data.
• Folded domains within simulated proteins maintain native contacts and exhibit dynamics consistent with all-atom simulations.

Conclusions:

• SOP-MULTI provides a powerful tool for studying the structural ensembles of complex multidomain proteins.
• The force field accurately models proteins with both folded and intrinsically disordered regions.
• SOP-MULTI is available as a LAMMPS-compatible package for broader research application.