In the era of personalized medicine, patients and physicians alike hope for refined therapies with improved efficacy and minimal side effects. Therapies such as Gleevec for CML, Rituximab for B-cell lymphomas, and now Ibrutinib for CLL have altered the paradigm of cancer treatment, and yet the standard of care for many cancers remain unchanged from decades ago. The complexity and size of biologic systems create challenges for the world of molecular modeling.  During my years as an undergraduate, under the guidance of Professor Shields, we tackled one such system. Our target was the Estrogen Receptor (ER), an important target in the most common type of breast cancer. We focused on creating a computational model of the ER derived from a high resolution crystal structure, docking various ligands with known IC50s, and then using molecular dynamic simulations to obtain the most favorable protein-ligand binding conformations that could then be processed to obtain binding enthalpies. Our model did not correlate well with published IC50s, but did exemplify a robust approach aimed at replicating in vitro testing, and has inspired continued interest in rationale drug design and a career in academic medicine.

From the computational chemistry lab to treating cancer: Inspiration for drug development in our time

249th National Meeting (2015)

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