Are AMBER Force Fields and Implicit Solvation Models Additive? A Folding Study with a Balanced Peptide Test Set.

Area of Science:

• Computational chemistry
• Biophysics
• Molecular dynamics

Background:

• Implicit solvation models aim to accelerate biomolecular simulations.
• The combined accuracy of independent force fields and solvation models for protein folding is unclear.
• Synergistic vs. additive effects of force field and solvation models require investigation.

Purpose of the Study:

• To test two implicit solvation models with recent protein force fields for predicting peptide secondary structure and folding.
• To assess the performance of various force field/solvent combinations using replica exchange molecular dynamics.
• To determine if force field and solvation effects are independent or synergistic.

Main Methods:

• Utilized the AMBER simulation package.
• Simulated five helical and five hairpin peptides (11-20 residues).
• Employed replica exchange molecular dynamics simulations with distinct starting configurations.

Main Results:

• No single force field/solvent combination accurately folded all tested peptides.
• Hairpin peptides proved more challenging to model than helical peptides.
• ff96/igb5* showed reasonable performance, while ff14SB/igb5* and ff14ipq/igb8 were better for helical and hairpin motifs, respectively.
• Salt bridge numbers were generally similar, with ff14ipq/igb8 slightly enhancing them.

Conclusions:

• The performance of force field and solvation models is interdependent with peptide secondary structure.
• Future efforts should consider co-developing implicit solvation models with force fields.
• Emerging coarse-graining strategies offer an alternative for modeling solvation effects.