Application of Machine Learning Techniques to Predict Binding Affinity for Drug Targets: A Study of Cyclin-Dependent Kinase 2

Curr Med Chem. 2021;28(2):253-265. doi: 10.2174/2213275912666191102162959.


Background: The elucidation of the structure of cyclin-dependent kinase 2 (CDK2) made it possible to develop targeted scoring functions for virtual screening aimed to identify new inhibitors for this enzyme. CDK2 is a protein target for the development of drugs intended to modulate cellcycle progression and control. Such drugs have potential anticancer activities.

Objective: Our goal here is to review recent applications of machine learning methods to predict ligand- binding affinity for protein targets. To assess the predictive performance of classical scoring functions and targeted scoring functions, we focused our analysis on CDK2 structures.

Methods: We have experimental structural data for hundreds of binary complexes of CDK2 with different ligands, many of them with inhibition constant information. We investigate here computational methods to calculate the binding affinity of CDK2 through classical scoring functions and machine- learning models.

Results: Analysis of the predictive performance of classical scoring functions available in docking programs such as Molegro Virtual Docker, AutoDock4, and Autodock Vina indicated that these methods failed to predict binding affinity with significant correlation with experimental data. Targeted scoring functions developed through supervised machine learning techniques showed a significant correlation with experimental data.

Conclusion: Here, we described the application of supervised machine learning techniques to generate a scoring function to predict binding affinity. Machine learning models showed superior predictive performance when compared with classical scoring functions. Analysis of the computational models obtained through machine learning could capture essential structural features responsible for binding affinity against CDK2.

Keywords: CDK2; Machine learning; cancer; drug design; kinase; mass-spring system.

Publication types

  • Review

MeSH terms

  • Cyclin-Dependent Kinase 2
  • Humans
  • Ligands
  • Machine Learning*
  • Molecular Docking Simulation
  • Pharmaceutical Preparations
  • Protein Binding
  • Supervised Machine Learning


  • Ligands
  • Pharmaceutical Preparations
  • Cyclin-Dependent Kinase 2