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Research Article

Terminus-immobilization effect on peptide conformations and peptide–peptide interactions

Wendi Luo1,2, Xiaocui Fang1,2, Chen Wang1,2,3, Yanlian Yang1,2, Bin Tu1,2( ), Qiaojun Fang1,2,3( )
Laboratory of Theoretical and Computational Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
University of Chinese Academy of Sciences, Beijing 100049, China
Sino-Danish Center for Education and Research, Beijing 101408, China
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Graphical Abstract

This study uses computational methods to understand the terminus-immobilization effect on peptide conformations and peptide–peptide interactions.

Abstract

Peptide-modified delivery systems are enabling the improvement of the targeting specificity, biocompatibility, stability, etc. However, the precise design of a peptide-decorated surface for a designated function has remained to be challenging due to a lack of mechanistic understanding of the interactions between surface-bound peptide ligands and their receptors. Enlightened by the recent report on pairwise interactions between peptides in the solution state and surface-immobilized state, we used computational simulations to explore the contributing mechanisms underlining the observed binding affinity characteristics. Molecular dynamics simulations were performed to sample and compare conformations of homo-octapeptides free in solution (mobile peptides) and bound to the surface (N-terminal fixed peptides). We found that peptides converged to more extended and rigid conformations when immobilized to the surface and confirmed that the extended structures could increase the space available to counter-interacting peptides during the peptide–peptide interactions. In addition, studies on interactions between stationary and mobile peptides revealed that main-chain/side-chain and side-chain/side-chain hydrogen bonds play an important role. The presented efforts in this work may provide supportive references for peptide design and modification on the nanoparticle surface as well as guidance for analyzing peptide–receptor interactions through an emphasis on hydrogen bonds during peptide design and an understanding of the influence on the binding affinity by the sequence-dependant conformational changes after peptide immobilization.

Keywords

terminus-immobilizationpeptide conformationspeptide–peptide interactionsmolecular dynamicspeptide design

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Nano Research
Volume 16 Issue 12,
December 2023
Pages 13498-13508
DOI: 10.1007/s12274-023-5787-7
Cite this article:
Luo W, Fang X, Wang C, et al. Terminus-immobilization effect on peptide conformations and peptide–peptide interactions. Nano Research, 2023, 16(12): 13498-13508. https://doi.org/10.1007/s12274-023-5787-7
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Received: 22 February 2023
Revised: 25 April 2023
Accepted: 29 April 2023
Published: 22 June 2023
© Tsinghua University Press 2023
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