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Topic

Study of Protein-Small Molecule Interaction via Nanoaperture Optical Tweezer

Department of Electrical and Computer Engineering

Date & location

• Tuesday, April 22, 2025

• 10:30 A.M.

• Engineering Office Wing

• Room 430

Reviewers

Supervisory Committee

• Dr. Reuven Gordon, Department of Electrical and Computer Engineering, University of Victoria (Supervisor)

• Dr. Makhsud Saidaminov, Department of Electrical and Computer Engineering, UVic (Member) 

   

External Examiner

• Dr. John Burke, Department of Biochemistry and Microbiology, University of Victoria 

Chair of Oral Examination

• Dr. Justin Albert, Department of Physics and Astronomy, UVic

   

Abstract

This thesis explores small molecule-protein interactions using nanoplasmonic op tical tweezers. Since their inception by Ashkin, optical tweezers have been widely adopted in biology due to their unique ability to manipulate nanoscale objects. The transcriptional activity of a single RNA polymerase molecule has been measured using dual optical tweezers and DNA tethering, revealing key processes such as transcriptional stepping, pausing, backtracking, and termination. However, tether-free nanoscale trapping remains challenging with single-beam optical tweezers, as trapping forces decrease disproportionately with target size reduction. A major breakthrough occurred with the development of subwavelength apertures for field enhancement, enabling trapping of free solution single proteins. Our lab specifically employs double nanohole apertures to generate a highly confined gradient field, facilitating stable trapping at the nanoscale. Abnormal protein phosphorylation plays a critical role in chronic illnesses such as Alzheimer’s disease, cancer, and arthritis. Consequently, both kinase and phosphatase therapeutics have become major areas of research. While numerous kinase inhibitors have received FDA approval, phosphatase-targeting drugs have faced significant challenges due to difficulties in identifying effective and selective binding sites. This thesis explores a promising phosphatase-targeting cancer therapeutic candidate using subwavelength-assisted optical tweezers. We present qualitative insights into the structural impact induced by small-molecule binding, complemented by molecular dynamics simulations. Additionally, we quantify binding affinity at both the single-molecule and ensemble levels.