Related Experiment Video

Updated: May 29, 2025

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

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Multiple ligands simultaneous molecular docking and dynamics approach to study the synergetic inhibitory of curcumin

La Ode Aman1, Netty Ino Ischak2, Teti Sutriyati Tuloli1

  • 1Department of Pharmacy, Faculty of Sport and Health, Universitas Negeri Gorontalo, Gorontalo, Indonesia.

Research in Pharmaceutical Sciences
|February 6, 2025
PubMed
Abstract

Insights

Two novel compounds, AC01 and AC02, show potential as ErbB4 inhibitors. Computational studies suggest they can act as anticancer agents individually or in combination with Lapatinib (FMM).

Area of Science:

  • Computational chemistry
  • Molecular modeling
  • Drug discovery

Background:

  • Lapatinib (FMM) and 5-fluorouracil (5-FU) are established anticancer drugs.
  • FMM targets tyrosine phosphorylation of ErbB4, while 5-FU inhibits cell proliferation.
  • ErbB4 is a key target in cancer therapy.

Purpose of the Study:

  • To investigate the ErbB4 inhibitory potential of AC01 and AC02.
  • To evaluate AC01 and AC02 as monotherapies and in combination with FMM.
  • To compare the efficacy of AC01/AC02-FMM combinations with the FMM-5-FU reference.

Main Methods:

  • Computational simulations including single and simultaneous ligand docking.
  • Molecular dynamics simulations for binding free energy calculations.
  • Analysis using AutoDockTools and gmx_MMPBSA.

Main Results:

  • 5-FU showed the lowest binding affinity; FMM showed the highest.
  • AC01 and AC02 bind to ErbB4, with overlapping positions to FMM-5-FU.
  • AC01 and AC02 occupy the ErbB4 activation loop, unlike 5-FU.
  • AC02 demonstrated slightly stronger binding to ErbB4 than AC01.

Conclusions:

  • AC01 and AC02 show promise as anticancer drug candidates.
  • These compounds exhibit potential for ErbB4 inhibition.
  • AC01 and AC02 may act synergistically with FMM for enhanced anticancer effects.
Keywords:
ErbB4Simultaneously molecular dockingSimultaneously molecular dynamics

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