Back to Search
Start Over
β-Hematin Crystal Formation: New Insights from Molecular Dynamics Simulations of Small Clusters in Condensed Phase
- Source :
- Crystal Growth & Design, Crystal Growth & Design, 2016, 16 (4), pp.2249-2259. ⟨10.1021/acs.cgd.6b00052⟩
- Publication Year :
- 2016
- Publisher :
- American Chemical Society (ACS), 2016.
-
Abstract
- International audience; Understanding the driving forces observed during the first steps of beta-hematin crystal formation is vital in view of developing new therapeutic treatments against malaria. In this context a new additive Amber force field specific to the cyclic dimer of ferriprotoporphyrin IX coordinated via Fe-O propionate bonds (FPD) was developed and validated in the context of a crystal model. The structure and dynamics of small clusters or oligomers of the FPD entity were studied by molecular dynamics in condensed phase. New hydrogen bond patterns were identified in the dynamical process of the simulations: the characteristic pair of coplanar hydrogen bonds reported in crystallographic structures between FPD sheets (Pagola et al. Nature 2000, 404, 307) is found to be in a subtle equilibrium with new hydrogen bonds between FPD located within the same sheet. Hydrophobic interactions appeared to play a key role in oligomer cohesion: clusters with intersheet hydrogen bonds are found unstable compared to clusters with embedded-type molecular systems. We propose that oligomers enclosing this kind of embedded structure could serve as elementary building motifs for crystal growth in the digestive vacuole of Plasmodium, and could represent an attractive target for impairing hemozoin formation in a therapeutic approach.
- Subjects :
- 0301 basic medicine
Hydrogen bond
[SDV]Life Sciences [q-bio]
Dimer
General Chemistry
010402 general chemistry
Condensed Matter Physics
01 natural sciences
Oligomer
Force field (chemistry)
0104 chemical sciences
law.invention
Hydrophobic effect
03 medical and health sciences
chemistry.chemical_compound
Crystallography
Molecular dynamics
030104 developmental biology
chemistry
law
Crystal model
General Materials Science
Crystallization
Subjects
Details
- ISSN :
- 15287505 and 15287483
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Crystal Growth & Design
- Accession number :
- edsair.doi.dedup.....8f434b638c2d60c3ce30de497c17ca9e