PMID- 36500509
OWN - NLM
STAT- MEDLINE
DCOM- 20221216
LR  - 20221221
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 27
IP  - 23
DP  - 2022 Dec 1
TI  - Structural Investigation of DHICA Eumelanin Using Density Functional Theory and 
      Classical Molecular Dynamics Simulations.
LID - 10.3390/molecules27238417 [doi]
LID - 8417
AB  - 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-eumelanin corresponding 
      to physiological pH, and (3) a binary mixture of both of the above 
      protomolecules. In the case of uncharged DHICA-eumelanin, spontaneous aggregation 
      occurred and water molecules were present inside the aggregates. In the systems 
      corresponding to physiological pH, all the carboxyl groups are negatively charged 
      and the DHICA-eumelanin model has a net charge of -4. The effect of K+ ions as 
      counterions was investigated. The results show high probability of binding to the 
      deprotonated oxygens of the carboxylate anions in the PTCA moiety. Furthermore, 
      the K+ counterions increased the solubility of DHICA-eumelanin in its charged 
      form. A possible explanation is that the charged protomolecules favor binding to 
      the K+ ions rather than aggregating and binding to other protomolecules. The 
      binary mixtures show aggregation of uncharged DHICA-eumelanins; unlike the 
      charged systems with no aggregation, a few charged DHICA-eumelanins are present 
      on the surface of the uncharged aggregation, binding to the K+ ions.
FAU - Soltani, Sepideh
AU  - Soltani S
AUID- ORCID: 0000-0001-5436-641X
AD  - Department of Physics and Astronomy, The University of Western Ontario, 1151 
      Richmond Street, London, ON N6A 3K7, Canada.
FAU - Sowlati-Hashjin, Shahin
AU  - Sowlati-Hashjin S
AUID- ORCID: 0000-0001-6968-1535
AD  - Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, 
      Canada.
FAU - Tetsassi Feugmo, Conrard Giresse
AU  - Tetsassi Feugmo CG
AUID- ORCID: 0000-0002-8992-4335
AD  - Department of Chemistry, University of Waterloo, 200 University Ave. West, 
      Waterloo, ON N2L 3G1, Canada.
FAU - Karttunen, Mikko
AU  - Karttunen M
AUID- ORCID: 0000-0002-8626-3033
AD  - Department of Physics and Astronomy, The University of Western Ontario, 1151 
      Richmond Street, London, ON N6A 3K7, Canada.
AD  - Department of Chemistry, The University of Western Ontario, 1151 Richmond Street, 
      London, ON N6A 5B7, Canada.
LA  - eng
GR  - Canada Research Chairs/
GR  - Natural Sciences and Engineering Research Council/
PT  - Journal Article
DEP - 20221201
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Melanins)
RN  - 0 (Pyrroles)
RN  - 0 (Polymers)
SB  - IM
MH  - *Molecular Dynamics Simulation
MH  - Density Functional Theory
MH  - *Melanins/metabolism
MH  - Pyrroles/analysis
MH  - Polymers/analysis
MH  - Hair/chemistry
PMC - PMC9738096
OTO - NOTNLM
OT  - 5,6-dihydroxyindole-2-carboxylic acid (DHICA)
OT  - Molecular Dynamics (MD) simulations
OT  - density functional theory (DFT)
OT  - eumelanin
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/12 06:00
MHDA- 2022/12/15 06:00
PMCR- 2022/12/01
CRDT- 2022/12/11 01:28
PHST- 2022/10/28 00:00 [received]
PHST- 2022/11/21 00:00 [revised]
PHST- 2022/11/22 00:00 [accepted]
PHST- 2022/12/11 01:28 [entrez]
PHST- 2022/12/12 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/12/01 00:00 [pmc-release]
AID - molecules27238417 [pii]
AID - molecules-27-08417 [pii]
AID - 10.3390/molecules27238417 [doi]
PST - epublish
SO  - Molecules. 2022 Dec 1;27(23):8417. doi: 10.3390/molecules27238417.