来自国家纳米科学中心、复旦大学的研究人员在《美国化学会志》（JACS）上合作发表了题为“Sequence Effects on Peptide Assembly Characteristics Observed by Using Scanning Tunneling Microscopy”的研究论文，通过扫描隧道显微技术（STM）来研究氨基酸序列对多肽组装结构及其稳定性的影响。
图摘自论文，表示利用STM进行多肽序列识别结果
来自国家纳米科学中心的研究人员利用STM技术在单分子水平上研究多肽的组装及其调控，已经发表了一系列的工作。他们在2011年利用STM确认了淀粉样多肽组装和聚集的核心片段及折叠位点，对于研究非结晶蛋白的组装结构提供了一种新颖的解析方法（Proc. Natl. Acad. Sci. USA, 2011, 108, 19605等），但是由于多肽在表面组装构象的多样性以及吸附稳定性的差异，利用STM进行多肽中氨基酸序列的识别仍具有极大的挑战性。
在本研究中，研究人员利用STM结合分子动力学模拟，研究了氨基酸残基序列对嵌段模型多肽在固体表面的吸附构象稳定性的影响，发现STM图像中的衬度差异与模型多肽中的序列具有关联性，同时分子动力学模拟发现不同氨基酸残基与石墨表面的结合能差异与衬度差异也具有一致性，说明了多肽序列对组装构象和组装特性的影响，暗示了利用STM进行多肽序列识别的可能性。此研究有助于深入理解多肽组装过程中侧基结构、序列等对组装过程、组装驱动力以及组装结构的影响。
此工作得到了科技部重大研究计划和基金委重大研究计划的支持。
DOI: 10.1021/ja307198u
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Sequence Effects on Peptide Assembly Characteristics Observed by Using Scanning Tunneling Microscopy
Xiaobo Mao, Yuanyuan Guo, Yin Luo, Lin Niu， Lei Liu, Xiaojing Ma, Huibin Wang, Yanlian Yang, Guanghong Wei and Chen Wang.
Homogeneous assemblies of the model peptides at interfaces have been achieved and observed with scanning tunneling microscopy. The dependence of the observed brightness in STM images is analyzed, and the correlation with the peptide residues is proposed. We have also investigated the conformational dynamics of the peptide assemblies adsorbed on a graphene sheet by performing all-atom molecular dynamic simulations in water at 300 K. The simulation results of the two peptide assemblies on graphite surfaces show that R4G4H8 and F4G4H8 peptide assemblies are mostly in β-sheet structure, and the interaction energy of the four different residues with graphite surfaces follows the order of Phe > His > Arg > Gly, consistent with their brightness contrasts in STM images. The insight on the distribution of residue moieties in the peptide assemblies could provide beneficial venues for studying peptide-based interfacial processes such as site-specific interactions between molecular species with peptides.
