scholarly journals Second harmonic generation polarization microscopy as a tool for protein structure analysis

2018 ◽  
Author(s):  
Junichi Kaneshiro ◽  
Yasushi Okada ◽  
Tomohiro Shima ◽  
Mika Tsujii ◽  
Katsumi Imada ◽  
...  
Keyword(s):  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Conformational Changes ◽  
Second Harmonic ◽  
Coherent Scattering ◽  
Polarization Measurement ◽  
Molecular Structures ◽  
Polarization Microscopy ◽  
Protein Structure Analysis ◽  
Macromolecular Protein

AbstractSecond-harmonic generation (SHG) is a nonlinear coherent scattering process that is sensitive to molecular structures in illuminated materials. We report SHG polarization measurement for the detection of protein conformational changes in solutions of macromolecular protein assemblies such as microtubules and protein crystals. The results illustrate the potential of this method for protein structural analysis in physiological solutions at room temperature without labelling.

scholarly journals Second harmonic generation polarization microscopy as a tool for protein structure analysis

2019 ◽  
Vol 16 (0) ◽  
pp. 147-157 ◽  
Author(s):  
Junichi Kaneshiro ◽  
Yasushi Okada ◽  
Tomohiro Shima ◽  
Mika Tsujii ◽  
Katsumi Imada ◽  
...  
Keyword(s):  
Protein Structure ◽  
Second Harmonic Generation ◽  
Structure Analysis ◽  
Harmonic Generation ◽  
Second Harmonic ◽  
Polarization Microscopy ◽  
Protein Structure Analysis

scholarly journals Modeling Conformational Changes in Proteins Based on Second Harmonic Generation Data

2019 ◽  
Vol 116 (3) ◽  
pp. 334a
Author(s):  
Seth D. Axen ◽  
Bason Clancy ◽  
Joshua Salafsky ◽  
Andrej Sali
Keyword(s):  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Conformational Changes ◽  
Second Harmonic

scholarly journals Discovery of fragments inducing conformational effects in dynamic proteins using a second-harmonic generation biosensor

RSC Advances ◽  
2021 ◽  
Vol 11 (13) ◽  
pp. 7527-7537
Author(s):  
Edward A. FitzGerald ◽  
Margaret T. Butko ◽  
Pierre Boronat ◽  
Daniela Cederfelt ◽  
Mia Abramsson ◽  
...  
Keyword(s):  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Conformational Changes ◽  
Second Harmonic ◽  
Conformational Effects

Fragments inducing conformational changes identified at a dynamic region of AChBP.

scholarly journals Protein Conformational Changes Are Detected and Resolved Site Specifically by Second-Harmonic Generation

2015 ◽  
Vol 109 (4) ◽  
pp. 806-815 ◽  
Author(s):  
Ben Moree ◽  
Katelyn Connell ◽  
Richard B. Mortensen ◽  
C. Tony Liu ◽  
Stephen J. Benkovic ◽  
...  
Keyword(s):  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Conformational Changes ◽  
Second Harmonic ◽  
Protein Conformational Changes

scholarly journals Second harmonic generation detection of Ras conformational changes and discovery of a small molecule binder

2019 ◽  
Vol 116 (35) ◽  
pp. 17290-17297 ◽  
Author(s):  
Elizabeth Donohue ◽  
Sina Khorsand ◽  
Gabriel Mercado ◽  
Kristen M. Varney ◽  
Paul T. Wilder ◽  
...  
Keyword(s):  
Second Harmonic Generation ◽  
Harmonic Generation ◽  
Small Molecule ◽  
Conformational Changes ◽  
High Throughput Screening ◽  
Quantum Coherence ◽  
Second Harmonic ◽  
Successful Implementation ◽  
Lung Cancers ◽  
Screening Platform

Second harmonic generation (SHG) is an emergent biophysical method that sensitively measures real-time conformational change of biomolecules in the presence of biological ligands and small molecules. This study describes the successful implementation of SHG as a primary screening platform to identify fragment ligands to oncogenic Kirsten rat sarcoma (KRas). KRas is the most frequently mutated driver of pancreatic, colon, and lung cancers; however, there are few well-characterized small molecule ligands due to a lack of deep binding pockets. Using SHG, we identified a fragment binder to KRasG12D and used 1H 15N transverse relaxation optimized spectroscopy (TROSY) heteronuclear single-quantum coherence (HSQC) NMR to characterize its binding site as a pocket adjacent to the switch 2 region. The unique sensitivity of SHG furthered our study by revealing distinct conformations induced by our hit fragment compared with 4,6-dichloro-2-methyl-3-aminoethyl-indole (DCAI), a Ras ligand previously described to bind the same pocket. This study highlights SHG as a high-throughput screening platform that reveals structural insights in addition to ligand binding.

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