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Updated: Mar 11, 2026

Using In Vitro Fluorescence Resonance Energy Transfer to Study the Dynamics Of Protein Complexes at a Millisecond Time Scale
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Using In Vitro Fluorescence Resonance Energy Transfer to Study the Dynamics Of Protein Complexes at a Millisecond Time Scale

Published on: March 14, 2019

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A molecular dynamics study of the binary complexes of APP, JIP1, and the cargo binding domain of KLC

Cooper A Taylor1, Bill R Miller2, Soleil S Shah1

  • 1Department of Chemistry, Gottwald Center for the Sciences, University of Richmond, Richmond, Virgina, 23173.

Proteins
|November 29, 2016
PubMed

Insights

Amyloid precursor protein (APP) transport by kinesin-1 light chain motor protein (KLC1) was computationally assessed. All tested KLC1, APP, and JIP1 complexes showed favorable binding, though KLC1:APP binding was less favorable due to APP flexibility.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Biophysics

Background:

  • Mutations in amyloid precursor protein (APP) lead to amyloid-beta peptides implicated in Alzheimer's disease and dementia.
  • Kinesin-1 light chain motor protein (KLC1) is hypothesized to transport APP, potentially interacting with JIP1.

Purpose of the Study:

  • To computationally assess the binding affinity of KLC1, APP, and JIP1 at the atomistic level.
  • To investigate the molecular interactions governing the transport of APP by KLC1.

Main Methods:

  • Molecular dynamics simulations were employed to analyze the interactions within binary complexes.
  • Free energy estimations were used to quantify the binding affinities of KLC1:APP, KLC1:JIP1, and APP:JIP1.

Main Results:

  • All binary complexes exhibited conformations with favorable binding free energies.
  • The KLC1:APP complex showed reduced binding favorability when considering approximate entropies, attributed to APP's flexibility.
  • Atomistic and residue-level driving forces for favorable interactions were identified in all complexes.

Conclusions:

  • The study provides the first atomistic computational assessment of KLC1, APP, and JIP1 interactions.
  • Favorable binding interactions exist between these proteins, offering insights into APP transport mechanisms relevant to neurodegenerative diseases.
Keywords:
APPAlzheimer's diseaseJIP1KLC1amyloid precursor proteinc-jun amino-terminal kinase-interacting protein 1kinesinkinesin light chain 1molecular dynamicsprotein-protein interactions

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