Part I: Molecular Dynamics Simulations to Explore the Plasticity of the Human Cytochrome P450 3A4 Enzyme. Part II: Probing the Conformational Transitions of Somatostatin Subtype-4 Receptor in order to Understand Ligand Agonism

Maria Kontoyianni, Southern Illinois University, Edwardsville

Usage Details

We will carry out two separate projects with distinct goals and deliverables. Specifically, Part I involves MD simulations on the P450 isoform 3A4, which metabolizes over one-third of drugs, in order to elucidate mechanistic details regarding diffusion patterns of metabolites, their exit pathways, and inhibitor binding. Consequently, the project is multidisciplinary spanning the fields of medicinal chemistry, biophysics, and computational chemistry.

We feel the project is appropriate for graduate students, while small subsections can be targeted by undergraduates in fields such as physics, engineering and chemistry. Our projected requirements are for one graduate student and one undergraduate.

Maria Kontoyianni is an expert in docking, has prior experience in P450s and membrane proteins, and will be responsible for setting up the system(s) and analyzing the results. Throughout her industrial career, prior to joining academia, she has had a solid record of successes using these methods for hit identification on therapeutic targets with measurable outcomes. She has continued in this area as an academic, and has published an extensive study on induced docking of CYP 3A4 substrates. Edward Ackad (collaborator) will be responsible for training students on using NAMD on Blue Waters, data management and data analysis. He is currently in possession of a Blue Waters Educational allocation for a separate project also using NAMD .