Presenter Profile
Masaru Miyagi
Associate Professor
Case Western Reserve University, Department of Pharmacology
Masaru Miyagi is a Professor in the Department of Pharmacology at the Case Western Reserve University and Director of the Cancer Metabolism Shared Resources at the Case Comprehensive Cancer Center. He received his Ph.D. in Biochemistry from Osaka University (Osaka, Japan) in 1997. Before joining Case Western Reserve University, Dr. Miyagi worked for Takara Shuzo Co. Ltd. as a research scientist, Cleveland Clinic Foundation as a post-doctoral fellow, and the University of North Dakota as an Assistant Professor. Dr. Miyagi’s research interests include the development of mass spectrometry-based methodologies for proteome and metabolome characterization. Dr. Miyagi has published more than 120 peer-reviewed scientific papers. Dr. Miyagi’s current research interests include 1) developing an analytical platform for identifying the targets of a drug, 2) developing a strategy for identifying isoAsp residues in proteins, and 3) establishing an analytical platform to monitor proteome and epigenome dynamics.
TALK TITLE
Using Machine Learning to Predict Unintended Drug-Implant Interactions
KEYWORDS
drugs, biomedical, materials, interactions, machine learning
ABSTRACT
Understanding how proteins function requires solving their structure and exploring their dynamic nature. Among the various analytical techniques available for studying protein structure and dynamics, mass spectrometry is a particularly valuable tool due to its high sensitivity and applicability to complex protein mixtures. Fifteen years ago, we pioneered the development of a structural mass spectrometry technique called "histidine hydrogen-deuterium exchange mass spectrometry (His-HDX-MS)."
This technique exploits the labile nature of the imidazole C2-hydrogen present in histidine residues, which exchanges with deuterium atoms when exposed to deuterium oxide (D2O) solvent. In His-HDX-MS, a protein or a mixture of proteins of interest is exposed to a deuterated solvent (D₂O) for a specific period of time and pD. After the HDX reaction, the protein(s) is digested into smaller peptides using enzymatic digestion (e.g., with trypsin), and the resulting peptides are analyzed using mass spectrometry. The extent of the HDX reaction as a function of pD yields a sigmoidal curve and the inflection point of the curve provides the pKa value of the His imidazole N-H group and the upper plateau of the curve indicates the solvent accessibility of the His imidazole group.
Thus, the method can probe both the electrostatic environment (from the pKa value) and solvent accessibility (from the HDX rate) of the individual histidine residues in proteins. Since its initial development, His-HDX-MS has gained widespread adoption within our group and other research teams as a valuable tool for investigating the dynamics of diverse proteins. In this presentation, we will provide an overview of our ongoing efforts in refining and expanding His-HDX-MS, along with the capabilities that this technique offers.