Conformational changes of single unmodified proteins by nanoaperture optical tweezers

Nanoaperture optical tweezers (NOTs) allow for trapping and studying the dynamics of individual proteins without the need for modifications like labels or tethers. The light scattering from the protein allows for extracting conformational changes, and this can be used to find the energy landscape of the protein. We use this approach to determine the energy landscape of Bovine Serum Albumin as it undergoes conformational changes, and the results are well-fit by transitiion state theory. We use this to find the maximum stability of the N state conformation as a function of temperature. This approach also allows for detecting changes that come from binding of small molecules, particularly drug candidates for restoring protein function.