Frontiers of Chemical Science and Engineering

, Volume 8, Issue 4, pp 433–444 | Cite as

Atomistic characterization of binding modes and affinity of peptide inhibitors to amyloid-β protein

  • Fufeng Liu
  • Wenjie Du
  • Yan Sun
  • Jie ZhengEmail author
  • Xiaoyan DongEmail author
Research Article


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.


Alzheimer’s disease amyloid β-protein peptide inhibitors protein-protein interaction molecular dynamics simulation 


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Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and TechnologyTianjin UniversityTianjinChina
  2. 2.Department of Chemical and Biomolecular EngineeringThe University of AkronAkronUSA
  3. 3.Collaborative Innovation Center of Chemical Science and Engineering (Tianjin)TianjinChina

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