Optimization of Protein–Protein Interaction Measurements for Drug Discovery Using AFM Force Spectroscopy
| Autor: | Niandong Jiao, Ruiguo Yang, Jing Hou, Lixin Dong, Amir Monemian Esfahani, Marc D. Basson, Bixi Zeng, Ning Xi, Zhiyong Sun, Lianqing Liu, Yongliang Yang, Liangliang Chen |
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| Rok vydání: | 2019 |
| Předmět: |
Materials science
Drug discovery High-throughput screening Force spectroscopy Nanotechnology 02 engineering and technology 021001 nanoscience & nanotechnology Small molecule Article 3. Good health Computer Science Applications Protein–protein interaction Nanosensor Nanobiotechnology Electrical and Electronic Engineering 0210 nano-technology Spectroscopy |
| Zdroj: | IEEE Transactions on Nanotechnology. 18:509-517 |
| ISSN: | 1941-0085 1536-125X |
| DOI: | 10.1109/tnano.2019.2915507 |
| Popis: | Increasingly targeted in drug discovery, protein-protein interactions challenge current high throughput screening technologies in the pharmaceutical industry. Developing an effective and efficient method for screening small molecules or compounds is critical to accelerate the discovery of ligands for enzymes, receptors and other pharmaceutical targets. Here, we report developments of methods to increase the signal-to-noise ratio (SNR) for screening protein-protein interactions using atomic force microscopy (AFM) force spectroscopy. We have demonstrated the effectiveness of these developments on detecting the binding process between focal adhesion kinases (FAK) with protein kinase B (Akt1), which is a target for potential cancer drugs. These developments include optimized probe and substrate functionalization processes and redesigned probe-substrate contact regimes. Furthermore, a statistical-based data processing method was developed to enhance the contrast of the experimental data. Collectively, these results demonstrate the potential of the AFM force spectroscopy in automating drug screening with high throughput. |
| Databáze: | OpenAIRE |
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