Related Experiment Video

Updated: May 15, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

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

Published on: October 26, 2015

Computational study and peptide inhibitors design for the CDK9 - cyclin T1 complex

Jelena Randjelović1, Slavica Erić, Vladimir Savić

  • 1Department of Organic Chemistry, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia.

Journal of Molecular Modeling
|January 9, 2013
PubMed

Insights

Researchers computationally designed peptides to inhibit the Cyclin-dependent kinase 9 (CDK9)/cyclin T1 complex, crucial for cell transcription and implicated in diseases like cancer and HIV. Three peptides showed promising binding properties for further therapeutic development.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Cyclin-dependent kinase 9 (CDK9) regulates cell transcription and is implicated in pathological processes like tumor growth and HIV-1 replication.
  • CDK9 activation involves the CDK9/cyclin T1 complex; inhibiting this complex is a potential therapeutic strategy.

Purpose of the Study:

  • To computationally design peptides targeting the CDK9/cyclin T1 interface for potential CDK9 inhibition.
  • To identify novel peptide inhibitors for diseases associated with aberrant CDK9 activity.

Main Methods:

  • Computational study of the CDK9/cyclin T1 interface.
  • Design of ten peptides based on complex analysis, hot spot residues, and fragment-based design.
  • Molecular docking, molecular dynamics simulations, MM-PBSA, and steered molecular dynamics (SMD) for binding affinity evaluation.

Main Results:

  • Three designed peptides (LQTLGF, ESIILQ, and PRWPE) demonstrated favorable binding properties to CDK9.
  • LQTLGF and ESIILQ were derived from cyclin T1, while PRWPE utilized fragment-based design.
  • These peptides represent promising candidates for further investigation as CDK9 inhibitors.

Conclusions:

  • Computational design and evaluation successfully identified potential peptide inhibitors of the CDK9/cyclin T1 complex.
  • The identified peptides offer a foundation for developing novel therapeutics against CDK9-related diseases.
  • Targeting the CDK9/cyclin T1 interface is a viable strategy for drug discovery.

More Related Videos

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

Related Concept Videos

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...
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...
Positive Regulator Molecules02:39

Positive Regulator Molecules

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.
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

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...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

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...