Physical Seminar Series: Yousuf Ramahi

Zoom Link: https://utoronto.zoom.us/j/84889438656
Meeting ID: 848 8943 8656
Passcode: pchemrocks

Identifying Allosterically Perturbed Residues at the Interleukin-7/Receptor Alpha Binding Interface

Abstract: Proteins are molecular machines whose dynamics dictate their myriad functions in the body. Protein dynamics and function are described by free energy landscapes, which represent the relative populations of conformational states. These landscapes can be perturbed by changes in the protein sequence or environment, which can alter the spatially distant correlated motions within the protein. Such long-range correlation is called protein allostery and forms the basis of protein functional motions. Allosteric modulation of protein function is an attractive approach for creating immunotherapy strategies. For example, the protein interleukin-7 (IL-7) modulates our immune system by binding to its receptor. Recent work in protein engineering suggests that IL-7’s binding affinity can be allosterically modulated by pre-binding to an antibody: however, there is limited structural or dynamic basis for these effects. This precludes precise control over the energy landscape, and thus function of IL-7. Our goal is to quantify the structural and dynamic changes to IL-7 when bound to antibody partners, to provide the mechanism by which binding affinity is altered. To query the allosteric effects of binding partners on IL-7’s structure and dynamics, we performed extensive molecular dynamics simulations in the free and bound forms. This seminar will focus on one piece of this puzzle, rigorously identifying the binding interface between IL-7 and its receptor, providing the foundation for understanding IL-7’s altered binding affinity.

CHM 1490 Students, please see Quercus for full speaker schedule.