A transferable coarse-grained model for diphenylalanine: how to represent an environment driven conformational...

Area of Science:

• Computational Chemistry
• Biomolecular Modeling
• Molecular Dynamics

Background:

• Coarse-grained (CG) simulation models are crucial for studying biomolecular structure formation.
• Accurately representing environment-driven conformational changes (e.g., folding, aggregation) remains a significant challenge.
• Diphenylalanine exhibits distinct conformational transitions in bulk water versus at interfaces or upon aggregation.

Purpose of the Study:

• To investigate the transferability of CG models for biomolecular systems.
• To develop a single CG model capable of reproducing diphenylalanine's conformational behavior in different environments (bulk and interface).
• To analyze the influence of interface properties on peptide conformational dynamics.

Main Methods:

• Development and application of a novel coarse-grained (CG) simulation model.
• Parameterization of nonbonded interactions based on solvation free energies of representative small molecules.
• Investigation of diphenylalanine conformational transitions in bulk water and at the cyclohexane/water interface.

Main Results:

• A single CG model successfully reproduced diphenylalanine's trans-to-cis conformational transition in both bulk and interface conditions.
• The model accurately captured the segregation of hydrophobic and hydrophilic components at the interface.
• The cyclohexane/water interaction potential significantly, though indirectly, influenced the peptide's conformational behavior.

Conclusions:

• A unified CG model can effectively represent environment-dependent conformational changes in peptides.
• Careful balancing of bonded and nonbonded interactions is critical for CG model accuracy.
• Subtle modifications in CG models can lead to significant alterations in predicted thermodynamic and conformational properties.