We report the scanning probe microscopy (SPM)-based single-molecule recognition of biomolecular interaction between protein kinase and small molecule (e.g. ATP or imatinib). In general, conventional atomic force microscopy (AFM) is unable to sense and detect the small ligand bound to a protein kinase due to its limited resolution for detecting the miniscule change in molecular shape for protein kinase driven by ligand-binding. However, in this study, we have first demonstrated that Kelvin probe force microscopy (KPFM) enables the recognition of a single protein kinase that interacts with a ligand (i.e. protein-ligand binding) at single-molecule resolution due to its ability to measure a change in the surface potential of a protein kinase induced by ligand-binding. Moreover, the measured surface potentials of protein kinases bound to ligands allows for quantitative understanding of ligand-binding mechanisms, which may be compared with theoretical/computational predictions on ligand-binding. Our study sheds light on KPFM that permits the precise recognition of single-molecule interactions, which opens a new avenue for the design and development of novel molecular therapeutics.

Single-molecule recognition of biomolecular interaction based on Kelvin probe force microscopy

243rd National Meeting (2012)

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