WFU Physics Colloquium

TITLE: Binding NEMO: Adventures in Molecular Dynamics

SPEAKER: Ryan Godwin

TIME: Monday April 17, 2017 at 3:00 PM

PLACE: Olin 101

Molecular dynamics is an indispensable tool for dissecting atomic-level interactions of critical physiological macromolecules. Simulations offer sufficient detail for hypothesizing mechanisms of action, proposing experimental mutations to disrupt or restore function, and elucidating how small changes to primary sequences differentiate structure and dynamics. After providing background on the biological motivation, we discuss simulation techniques, analysis methods, and relevant biological hypotheses. Most of the talk will focus on the zinc finger of NEMO, a CYS3HIS1 zinc-coordinating protein, a binding partner of ubiquitin that regulates critical cellular processes like immune responses and apoptosis. We investigate how the protonation states of the zinc-binding cysteines impact the protein's behavior and influence zinc complexation and the importance of long simulations to tease out additional insights. Following that, we compare the wild-type zinc finger with two homologous, disease-associated proteins to discern details underlying malfunction. Lastly, we discuss single point mutations in the core of tRNA^MET and their effect on allosteric properties of the biopolymer by analyzing hydrogen bonds and correlated motions using network-based techniques to investigate connections within structure and dynamics, respectively.