Atomistic modeling of peptides bound to a chemically active surface: conformational implications

Area of Science:

• Computational chemistry
• Molecular modeling
• Surface science

Background:

• Modeling flexible molecules on surfaces is crucial for understanding biological interactions.
• Previous methods modeled inert surfaces, neglecting crucial peptide-surface interactions.
• High-density peptide tethering requires accurate microstructural generation.

Purpose of the Study:

• To develop and validate a computational strategy for modeling flexible peptides on metallic surfaces.
• To investigate the impact of peptide-surface interactions on peptide conformation.
• To compare simulations with and without considering chemical surface activity.

Main Methods:

• Adaptation of a prior computational procedure for inert surfaces.
• Atomistic-level simulation of uncorrelated relaxed microstructures.
• Testing the strategy with CREKA (Cys-Arg-Glu-Lys-Ala) pentapeptide on a gold surface.

Main Results:

• The computational strategy successfully models high densities of tethered peptides.
• Peptide-surface interactions correlate with the overall conformational profile of CREKA.
• Side chain orientation is affected by surface interactions, while main chain conformation remains largely unchanged.

Conclusions:

• The developed computational strategy accurately models flexible peptides on metallic surfaces.
• Peptide-surface chemical interactions play a role in determining peptide conformation.
• The bioactive conformation of CREKA remains favored, irrespective of surface interactions.