This seminar will discuss our undergraduate research team’s work on the MEK1 signaling protein. MEK1 is a protein kinase in the MAPK cellular signaling pathway and is notable for its dual-specificity and its potential as a drug target for a variety of cancer therapies. While much is known about the key role of MEK1 in signaling events, understanding of the structural features that sustain MEK1 function remain limited due to absence of crystal or NMR structural insights into the phosphorylated and activated form of MEK1. In this work, homology modeling is used to overcome this limitation and generate computational models of the doubly-phosphorylated active MEK1 conformation. A variety of models were generated using crystal structures of active protein kinases as homology model templates. These models were equilibrated using molecular dynamics simulations, and each model was validated against several known structural characteristics of activated kinases. The best model structures were used in docking studies with ATP and a small peptide sequence that represents the activation loop of ERK2 to identify the most important residues in stabilizing protein docking and phosphorylation. These results provide insights for the pursuit of structure guided mutagenesis and drug design.
The seminar will also discuss some of Dr. McDonald’s other professional activities, including her work with the Molecular Sciences Software Institute, her interest in best practices for teaching programming in the chemistry curriculum, and her efforts to enhance diversity in computational chemistry.
Dr. McDonald received her Ph.D. from Georgia Tech in 2009 with the Sherrill Group. After completing a post-doc at the University of Maryland School of Pharmacy, Dr. McDonald joined the faculty in the department of Chemistry & Biochemistry at California Polytechnic State University in 2011. She was tenured and promoted to associate professor at Cal Poly in 2017. Cal Poly is a large, public primarily undergraduate university that is one of the 23 campuses in the California State University System.