Structural Investigation of DHICA Eumelanin Using Density Functional Theory and Classical Molecular Dynamics...

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Computational Biophysics

Background:

• Eumelanin, a key pigment in various tissues, is a complex polymer primarily composed of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI) units.
• DHICA is the predominant building block in natural eumelanin, forming protomolecules with indole-2-carboxylic acid-5,6-quinone (ICAQ) and pyrrole-2,3,5-tricarboxylic acid (PTCA).

Purpose of the Study:

• To investigate the self-assembly behavior of DHICA-eumelanin protomolecules in aqueous solutions using molecular dynamics (MD) simulations.
• To explore the influence of molecular charge and counterions (K+) on DHICA-eumelanin aggregation and solubility at various concentrations.

Main Methods:

• Multi-microsecond molecular dynamics (MD) simulations were employed to model DHICA-eumelanin self-assembly.
• Density functional theory (DFT) calculations were used for initial parameterization of the DHICA-eumelanin protomolecule.
• Simulations were conducted on uncharged DHICA-eumelanin, charged DHICA-eumelanin (physiological pH), and binary mixtures.

Main Results:

• Uncharged DHICA-eumelanin spontaneously aggregated in aqueous solution, trapping water molecules within the aggregates.
• Charged DHICA-eumelanin (net charge of -4) exhibited increased solubility in the presence of K+ counterions, which preferentially bound to carboxylate groups.
• Binary mixtures showed aggregation of uncharged protomolecules, with charged protomolecules associating with the surface of these aggregates via K+ ions.

Conclusions:

• The charge state of DHICA-eumelanin significantly impacts its self-assembly and solubility in aqueous environments.
• Potassium ions play a crucial role in solubilizing charged DHICA-eumelanin by interacting with its carboxylate moieties, preventing aggregation.
• These findings provide insights into the structural organization and solution behavior of eumelanin, relevant for its biological functions and potential applications.