Session: COMP Poster Session:

Endocrine disrupting chemicals (EDCs) bind to the androgen receptor (AR) and dysregulate its function, resulting in deleterious effects in humans. The current hypothesis suggests EDCs bind directly to the steroid binding site and disrupt its function. Yet, new data indicates that EDCs may exert allosteric effects on AR by binding to the surface site, binding function-3 (BF-3). This study investigated the effect that 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene) (DDE) binding to BF-3 has on the stability of bound dihydrotestosterone (DHT). The CHARMM General Force Field (CGenFF) was employed to develop parameters for CHARMM based molecular dynamic (MD) simulations. The DDE parameters were supplemented into the CHARMM force field to run six 1 μs simulations of the AR-steroid complex with DDE docked in the BF-3 site. RMSD and RMSF analysis revealed structural variations between the systems with DDE and the control. The residues near DHT had increased mobility, while the residues near DDE were less mobile. Further studies will measure binding and dissociation energies of DHT via random accelerated and steered MD simulations.

Evangelia Kotsikorou

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