biostudies-literatureUnknown27(23)Soltani SEumelanin is an important pigment, for example, in skin, hair, eyes, and the inner ear. It is a highly heterogeneous polymer with 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI) building blocks, of which DHICA is reported as the more abundant in natural eumelanin. The DHICA-eumelanin protomolecule consists of three building blocks, indole-2-carboxylic acid-5,6-quinone (ICAQ), DHICA and pyrrole-2,3,5-tricarboxylic acid (PTCA). Here, we focus on the self-assembly of DHICA-eumelanin using multi-microsecond molecular dynamics (MD) simulations at various concentrations in aqueous solutions. The molecule was first parameterized using density functional theory (DFT) calculations. Three types of systems were studied: (1) uncharged DHICA-eumelanin, (2) charged DHICA-eumeMolecules (Basel, Switzerland)8417https://www.ebi.ac.uk/biostudies/studies/S-EPMC9738096biostudies-literatureStructural Investigation of DHICA Eumelanin Using Density Functional Theory and Classical Molecular Dynamics Simulations.PMC9738096Sowlati-Hashjin SKarttunen MSoltani STetsassi Feugmo CGfalseStructural Investigation of DHICA Eumelanin Using Density Functional Theory and Classical Molecular Dynamics Simulations.Eumelanin is an important pigment, for example, in skin, hair, eyes, and the inner ear. It is a highly heterogeneous polymer with 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI) building blocks, of which DHICA is reported as the more abundant in natural eumelanin. The DHICA-eumelanin protomolecule consists of three building blocks, indole-2-carboxylic acid-5,6-quinone (ICAQ), DHICA and pyrrole-2,3,5-tricarboxylic acid (PTCA). Here, we focus on the self-assembly of DHICA-eumelanin using multi-microsecond molecular dynamics (MD) simulations at various concentrations in aqueous solutions. The molecule was first parameterized using density functional theory (DFT) calculations. Three types of systems were studied: (1) uncharged DHICA-eumelanin, (2) charged DHICA-eume2022-01-01T00:00:00Z2022 Dec2025-04-20T03:35:57.153Z2025-04-20T03:35:57.153ZS-EPMC97380963650050910.3390/molecules27238417