HyRes: a coarse-grained model for multi-scale enhanced sampling of disordered protein conformations

Area of Science:

• Computational Biology
• Biophysics
• Protein Dynamics

Background:

• Multi-scale enhanced sampling (MSES) couples coarse-grained (CG) models with atomistic force fields to accelerate simulations.
• This approach is promising for studying intrinsically disordered proteins (IDPs), which lack stable structures.
• Efficient CG models are crucial for MSES to accurately capture atomistic fluctuations.

Purpose of the Study:

• To develop a novel hybrid resolution CG model (HyRes) for MSES simulations of IDPs.
• To ensure HyRes captures both local (secondary structure) and long-range interactions relevant to IDPs.
• To enhance the efficiency and accuracy of atomistic conformational sampling for IDPs.

Main Methods:

• HyRes features an atomistic backbone and intermediate-resolution side chains.
• Secondary structure propensities are tuned via backbone hydrogen bonding and torsion profiles.
• Side chain parameters and interactions are optimized using atomistic simulations and protein databases.

Main Results:

• HyRes simulations show faster atomistic structural transitions compared to Cα-only Gō-like models.
• The new model increases the convergence rate of MSES simulations for small IDPs.
• HyRes provides semi-quantitative secondary structure propensities and qualitative long-range interactions.

Conclusions:

• The HyRes model offers improved efficiency for MSES simulations of IDPs.
• Further optimization could enhance its utility for larger, more complex IDPs.
• This CG model has the potential to advance the study of IDPs in cellular signaling and regulation.