Collaborative Approach between Explainable Artificial Intelligence and Simplified Chemical Interactions to Explore
Tomomi Shimazaki1, Masanori Tachikawa2
1Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Yokohama, Kanagawa 236-0027, Japan.
ACS Omega
|April 6, 2022
Summary
This study combines explainable artificial intelligence (AI) with simplified chemical scores to enhance virtual screening for drug discovery. The approach efficiently identifies active drug ligands for cancer target protein cyclin-dependent kinase 2 (CDK2).
Area of Science:
- Computational chemistry
- Drug discovery
- Artificial intelligence in medicine
Background:
- Virtual screening is crucial for identifying potential drug candidates.
- Traditional docking simulations struggle to differentiate active ligands from decoys.
- Cyclin-dependent kinase 2 (CDK2) is a significant target protein in cancer therapy.
Purpose of the Study:
- To develop an improved virtual screening method for drug discovery.
- To enhance the efficiency and accuracy of identifying active ligands.
- To apply explainable AI (AI) and simplified scoring functions to target CDK2.
Main Methods:
- Employing machine learning models integrated with simplified scoring functions.
- Utilizing simplified Coulomb and Lennard-Jones interaction scores.
- Applying explainable AI to analyze ligand-receptor interactions.
Main Results:
- Simplified interaction scores significantly improved machine learning model classification.
- The combined approach demonstrated enhanced ability to identify active ligands.
- Explainable AI successfully highlighted key CDK2 residues involved in ligand recognition.
Conclusions:
- The collaborative approach of explainable AI and simplified scoring functions is effective for virtual screening.
- This method offers a more efficient and accurate way to discover drug candidates.
- The findings provide insights into CDK2-ligand interactions for cancer drug development.
More Related Videos
11:11Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach
Published on: February 21, 2019
7.6K
09:39Exploring Biomolecular Interaction Between the Molecular Chaperone Hsp90 and Its Client Protein Kinase Cdc37 using Field-Effect Biosensing Technology
Published on: March 31, 2022
3.4K
Related Concept Videos
02:39Positive Regulator Molecules
5.7K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.7K
02:15M-Cdk Drives Transition Into Mitosis
5.7K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.7K
00:50Anaphase Promoting Complex
3.0K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.0K
02:40Ligand Binding Sites
13.7K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
13.7K
02:34Inhibition of Cdk Activity
5.0K
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...
5.0K
02:04Protein-protein Interfaces
13.9K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
13.9K