Chemists from RUDN University, in collaboration with Chinese researchers, employed a combination of machine learning and molecular modeling to uncover potential drugs that can inhibit the enzyme responsible for uncontrolled cell division. Their findings were published in Biomedicines.
The enzyme in question, Cyclin-dependent kinase 2 (CDK 2), plays a significant role in regulating cell division, particularly in cancer cells. Inhibiting CDK 2 activity is crucial in restraining tumor growth. These scientists utilized computer-based techniques, specifically machine learning and molecular modeling, to identify potential CDK 2 inhibitors.
“Cyclin-dependent kinase 2 holds promise as a target for cancer treatment. Developing inhibitors for this enzyme is a critical aspect of anti-tumor therapy. While the enzyme’s role in tumor formation is not fully understood, its inhibition has demonstrated effectiveness in cancer treatment. While some inhibitors have undergone clinical trials, a selective inhibitor tailored to this enzyme is yet to be found,” explained Alexander Novikov, Ph.D. in Chemistry, a senior researcher at the Joint Institute of Chemical Research at RUDN University.
To identify potential drug candidates, the team employed machine learning models. Multiple models were constructed to identify active CDK 2 inhibitors. Molecular docking, a technique that identifies the most favorable molecular configuration for forming a stable complex, was used to build a molecular model.
The machine learning models identified 25 potential active CDK 2 inhibitors with an impressive 98% accuracy. These candidates were subsequently tested using molecular docking, and the top three compounds demonstrated superior performance. To further assess their stability and compactness, a computer simulation was conducted using the molecular dynamics method and compared with the reference compound dalpiciclib.
“In comparison to the control drug dalpiciclib, the three computed compounds exhibited increased stability and compactness. Despite these promising results, our study has certain limitations. Rigorous in vitro and in vivo clinical trials are required to confirm their inhibitory activity and potential therapeutic effectiveness. Furthermore, during drug development, it will be necessary to investigate the compounds’ impact on off-target interactions and assess their toxicity,” emphasized Alexander Novikov, Ph.D. in Chemistry, senior researcher at the Joint Institute of Chemical Research at RUDN University.