Related Experiment Video

Updated: Aug 4, 2025

Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.2K

Evaluation of autophagy inhibition to combat cancer: (vanadium complex)-protein interactions, parameterization, and

Taináh M R Santos1, Camila A Tavares2, Ander F Pereira3

  • 1Laboratory of Molecular Modelling, Department of Chemistry, Federal University of Lavras, /MG, Lavras, 37200-000, Brazil. tainah-martins@hotmail.com.

Journal of Molecular Modeling
|March 30, 2023
PubMed

Insights

This study developed AMBER force field parameters for a vanadium complex (VC) to simulate its interaction with PI3K, aiding autophagy inhibition research in pancreatic cancer. Findings support new metal complex parameterizations for biological applications.

Area of Science:

  • Computational Chemistry
  • Biophysics
  • Cancer Research

Background:

  • Autophagy plays a crucial role in cancer progression and presents therapeutic advantages over traditional chemotherapy.
  • Vanadium complexes (VC), specifically [VO(oda)(phen)], demonstrate inhibitory effects on autophagy in pancreatic cancer cells.
  • Molecular dynamics (MD) simulations are vital for understanding metal complex-biological target interactions, but require accurate force fields (FF).

Purpose of the Study:

  • To develop and validate AMBER force field parameters for the vanadium complex [VO(oda)(phen)] (VC).
  • To investigate the interaction between the parameterized VC and PI3K, a key target in autophagy.
  • To contribute to the understanding of autophagy inhibition mechanisms in pancreatic cancer.

Main Methods:

  • Density Functional Theory (DFT) calculations (B3LYP/def2-TZVP) to obtain the minimum energy structure of VC.
  • Development of AMBER force field parameters for VC.
  • Molecular dynamics (MD) simulations in vacuum and explicit solvent to validate the FF and study VC-PI3K interactions.
  • Root-mean-square deviation (RMSD) analysis to assess structural stability.
  • Molecular docking simulations.

Main Results:

  • Validated AMBER FF parameters for VC, showing good agreement with DFT calculations and experimental data for bond lengths and angles.
  • MD simulations demonstrated high structural stability with an average RMSD of 0.3%.
  • Docking and 120 ns MD simulations provided insights into the interaction between VC and PI3K.

Conclusions:

  • The developed FF parameters are suitable for simulating vanadium complexes in biological systems.
  • This work facilitates further computational studies on metal complexes for cancer therapy.
  • The findings advance the elucidation of autophagy inhibition by metal complexes, particularly in pancreatic cancer.
Keywords:
AMBER force fieldAutophagyDockingMolecular dynamicsVanadium complex

More Related Videos

The Lactate Dehydrogenase Sequestration Assay — A Simple and Reliable Method to Determine Bulk Autophagic Sequestration Activity in Mammalian Cells09:34

The Lactate Dehydrogenase Sequestration Assay — A Simple and Reliable Method to Determine Bulk Autophagic Sequestration Activity in Mammalian Cells

Published on: July 27, 2018

18.2K
Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

934

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
14.7K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.4K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.1K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K