Since our project focused on creating a detection system using an estrogen receptor, we modeled the estrogen receptor-oxybenzone binding interaction in order to better understand the binding mechanism of the two molecules. We used Pymol to model the receptor-ligand interactions between the oxybenzone (ligand) and the estrogen receptor. Through the use of computer simulation, we visually demonstrated how oxybenzone fits into the hER estrogen receptor compared to how estrogen fits into the receptor.
Initially, we looked at the binding of the human estrogen receptor ligand-binding domain in a complex with 17ß-estradiol (an estrogen molecule). Because estradiol, a form of estrogen, has similar characteristics to oxybenzone with regards to binding to the human estrogen receptor and therefore acting as an endocrine disruptor, we sought to align these two molecules to create a theoretical visualization of the process. We used the 1ERE structure in the Protein Data Bank (PDB) in our modeling, provided that it was our most viable structure. By importing the structure on PyMOL as a PDB file, a visual representation was attained. The receptor consisted of 6 chains, however, we chose to focus on only 2 chains for clarity and because estrogen receptors typically function as dimers [1].
We attained the oxybenzone structure file from PubChem. Then, we attempted to structurally align oxybenzone with estrogen through PyMOL, however, small molecule alignment was unsuccessful. We then used BCL::MolAlign to perform small molecule docking with the alignment of oxybenzone to estradiol [2]. Both files of the estradiol and oxybenzone were attained as an SDF file and inputted into Meiler Lab’s BCL::MolAlign Server. Alignment was performed with the fully-flexible alignment level, giving a more accurate representation of our model as opposed to rigid formation. The resulting file after running the job was then opened in PyMOL and adjusted for better visualization.
The results can be seen in the photos below. These modeling results are important in considering factors like binding strength and duration between the estrogen receptor and oxybenzone.
[1] Schrödinger, L., & DeLano, W. (2020). PyMOL. Retrieved from http://www.pymol.org/pymol
[2] Brown BP, Mendenhall JL, Meiler J; "BCL::MolAlign: Three-Dimensional Small Molecule Alignment for 2 Pharmacophore Mapping", JCIM February 2019