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Frontiers of Chemical Science and Engineering

ISSN 2095-0179

ISSN 2095-0187(Online)

CN 11-5981/TQ

Postal Subscription Code 80-969

2018 Impact Factor: 2.809

Front. Chem. Sci. Eng.    2014, Vol. 8 Issue (4) : 433-444    https://doi.org/10.1007/s11705-014-1454-6
RESEARCH ARTICLE
Atomistic characterization of binding modes and affinity of peptide inhibitors to amyloid-β protein
Fufeng LIU1,3,Wenjie DU1,Yan SUN1,3,Jie ZHENG2,3,*(),Xiaoyan DONG1,3,*()
1. Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
2. Department of Chemical and Biomolecular Engineering, The University of Akron, Akron, OH 44325, USA
3. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China
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Abstract

The aggregation of amyloid β-protein (Aβ) is tightly linked to the pathogenesis of Alzheimer’s disease. Previous studies have found that three peptide inhibitors (i.e., KLVFF, VVIA, and LPFFD) can inhibit Aβ aggregation and alleviate Aβ-induced neurotoxicity. However, atomic details of binding modes and binding affinities between these peptide inhibitors and Aβ have not been revealed. Here, using molecular dynamics simulations and molecular mechanics Poisson Boltzmann surface area (MM/PBSA) analysis, we examined the effect of three peptide inhibitors (KLVFF, VVIA, and LPFFD) on their sequence-specific interactions with Aβ and the molecular basis of their inhibition. All inhibitors exhibit varied binding affinity to Aβ, in which KLVFF has the highest binding affinity, whereas LPFFD has the least. MM/PBSA analysis further revealed that different peptide inhibitors have different modes of interaction with Aβ, consequently hotspot binding residues, and underlying driving forces. Specific residue-based interactions between inhibitors and Aβ were determined and compared for illustrating different binding and inhibition mechanisms. This work provides structure-based binding information for further modification and optimization of these three peptide inhibitors to enhance their binding and inhibitory abilities against Aβ aggregation.

Keywords Alzheimer’s disease      amyloid β-protein      peptide inhibitors      protein-protein interaction      molecular dynamics simulation     
Corresponding Author(s): Jie ZHENG   
Online First Date: 30 December 2014    Issue Date: 14 January 2015
 Cite this article:   
Wenjie DU,Yan SUN,Jie ZHENG, et al. Atomistic characterization of binding modes and affinity of peptide inhibitors to amyloid-β protein[J]. Front. Chem. Sci. Eng., 2014, 8(4): 433-444.
 URL:  
https://academic.hep.com.cn/fcse/EN/10.1007/s11705-014-1454-6
https://academic.hep.com.cn/fcse/EN/Y2014/V8/I4/433
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