TY - JOUR
T1 - Optimization of protein–protein interaction measurements for drug discovery using AFM force spectroscopy
AU - Yang, Yongliang
AU - Zeng, Bixi
AU - Sun, Zhiyong
AU - Esfahani, Amir Monemian
AU - Hou, Jing
AU - Jiao, Nian Dong
AU - Liu, Lianqing
AU - Chen, Liangliang
AU - Basson, Marc D.
AU - Dong, Lixin
AU - Yang, Ruiguo
AU - Xi, Ning
N1 - Publisher Copyright:
© 2019 IEEE.
PY - 2019
Y1 - 2019
N2 - 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 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 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.
AB - 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 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 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.
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U2 - 10.1109/TNANO.2019.2915507
DO - 10.1109/TNANO.2019.2915507
M3 - Article
AN - SCOPUS:85066821319
SN - 1536-125X
VL - 18
SP - 509
EP - 517
JO - IEEE Transactions on Nanotechnology
JF - IEEE Transactions on Nanotechnology
ER -