Rapidly determining the 3D structure of proteins by surface-enhanced Raman spectroscopy
Hao Ma, Sen Yan, Xinyu Lu, Yi‐Fan Bao, Jia Liu, Langxing Liao, Kun Dai, Maofeng Cao, Xiaojiao Zhao, Hao Yan, Hailong Wang, Xiaohui Peng, Ningyu Chen, Hui-Shu Feng, Lilin Zhu, Guangbao Yao, Chunhai Fan, De‐Yin Wu, Binju Wang, Xiang Wang, Bin Ren
Abstract
Despite great advances in protein structure analysis, label-free and ultrasensitive methods to obtain the natural and dynamic three-dimensional (3D) structures are still urgently needed. Surface-enhanced Raman spectroscopy (SERS) can be a good candidate, whereas the complexity originated from the interactions between the protein and the gradient surface electric field makes it extremely challenging to determine the protein structure. Here, we propose a deciphering strategy for accurate determination of 3D protein structure from experimental SERS spectra in seconds by simply summing SERS spectra of isolated amino acids in electric fields of different strength with their orientations in protein. The 3D protein structure can be reconstructed by comparing the experimental spectra obtained in a well-defined gap-mode SERS configuration with the simulated spectra. The gradient electric field endows SERS with a unique advantage to section biomolecules with atomic precision, which makes SERS a competent tool for monitoring biomolecular events under physiological conditions.