Martini3-IDP: improved Martini 3 force field for disordered proteins

Area of Science:

• Computational Biology
• Biophysics
• Structural Biology

Background:

• Coarse-grained molecular dynamics (CG MD) is crucial for simulating intrinsically disordered proteins (IDPs).
• The popular Martini model often produces overly compact IDP conformations, limiting its utility.
• Accurate simulation of IDPs is essential for understanding their diverse biological functions.

Purpose of the Study:

• To develop an improved coarse-grained model for intrinsically disordered proteins.
• To enhance the simulation accuracy of IDP conformations and interactions.
• To enable reliable simulations of IDPs in complex biological systems and at larger scales.

Main Methods:

• Optimized bonded parameters for the Martini 3 force field using atomistic simulations of diverse IDPs.
• Developed the Martini3-IDP model, focusing on expanded IDP conformations.
• Validated the model through comprehensive testing, including multidomain proteins, membrane binding, small molecule interactions, and biomolecular condensate formation.

Main Results:

• The Martini3-IDP model generates more expanded IDP conformations, accurately reproducing experimental radii of gyration.
• The model maintains the balanced interactions of the underlying Martini 3 force field.
• Successfully reproduced complex interactions of IDPs with membranes, small molecules, and phase-separated condensates.

Conclusions:

• The optimized Martini3-IDP model significantly improves the simulation of intrinsically disordered proteins.
• This enhanced model expands the applicability of coarse-grained simulations for IDPs in complex biological contexts.
• Enables exploration of IDP behavior at spatio-temporal scales beyond the reach of all-atom methods.