Developing Bonded Potentials for a Coarse-Grained Model of Intrinsically Disordered Proteins.

Area of Science:

• Computational Biology
• Biophysics
• Protein Science

Background:

• Coarse-grained (CG) models offer molecular insights into intrinsically disordered proteins (IDPs) and their phase separation.
• Existing CG models struggle to accurately represent secondary structures like helices in IDPs.

Purpose of the Study:

• To introduce a novel CG dihedral angle potential for accurately capturing transient helical structures in IDPs.
• To develop sequence-dependent parameters for improved IDP structural modeling.

Main Methods:

• Developed a CG dihedral angle potential using Cα atoms to model helical structures.
• Established Cα-based helix assignment rules for model validation.
• Parameterized the model using amino acid helical propensities and validated against NMR data.

Main Results:

• The new model successfully reproduces atomistic helicity results for peptides and folded proteins.
• Simulated helical propensities for IDPs show excellent agreement with NMR-based α-helix fractions.
• The HPS-SS model accurately captures key structural features of IDPs.

Conclusions:

• The HPS-SS model provides accurate structural insights into IDPs, including their helical content.
• This model is suitable for large-scale simulations of protein assembly due to its simplicity.
• Advances understanding of sequence determinants in IDP phase separation and biological condensate formation.