Developing a Nanopore Tweezer Toolkit for Analyzing Kinase Structural Dynamics and Screening Allosteric Inhibitors

Protein nanopores are powerful sensors that enable a new class of single-molecule measurements, with applications ranging from fundamental science to commercial DNA sequencing. Our focus is on developing and applying novel nanopore approaches to tackle challenges in protein analysis, ultimately improving disease diagnostics and therapeutics. In this project, we are creating innovative nanopore tweezers capable of real-time tracking kinase movements triggered by ligand or inhibitor binding at a 100-microsecond resolution for tens of minutes at the single-molecule level. This work will generate comprehensive energetic maps of the conformational states of disease-associated kinases during substrate binding, catalytic activity, allosteric regulation, and inhibition. Overall, this study will introduce new tools and opportunities for studying structural dynamics, single-molecule enzymology, drug discovery, and personalized precision medicine. Project Number: 1R01GM159415-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Min Chen | Institution: UNIVERSITY OF MASSACHUSETTS AMHERST, HADLEY, MA | Award Amount: $396,854 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 MCST-J (85)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11167050