Investigation of the newly characterized baimantuoluoamide a and baimantuoluoamide b alkaloids as potential cyclin-dependent kinase 4 (CDK4) inhibitors using molecular docking and molecular dynamics simulations

CDK4 is an enzyme often associated with various forms of cancer. Since an abnormal function of the CDK4-cyclin D1 protein complex can play a pivotal role in causing various types of cancer, CDK4 is considered an important therapeutic target. Traditionally, herbal medicines have played a vital role in the treatment of many diseases and ailments. Likewise, D. stramonium, Solanaceae, possesses the cytotoxic, antiinflammatory, anti-viral, antibacterial, antioxidant, analgesic, antiulcer, and insecticidal properties which are a result of its phytoconstituents. Baimantuoluoamide A and baimantuoluoamide B are newly isolated Datura metel L. phytoconstituents, whose molecular interactions are still unknown. Additionally, an experimentally determined crystal structure of baimantuoluoamide A and baimantuoluoamide B bound to CDK4 has not yet been reported. Thus, this study aimed to identify the residues in the baimantuoluoamide A and baimantuoluoamide B-CDK4 binding interface. For this purpose, molecular docking, molecular dynamics (MD) simulations and the MM/GBSA method to identify the binding modes and crucial residues were employed. The results obtained in the current study will provide valuable guidelines for developing novel potent and selective CDK4 inhibitors. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

CDK4 plays a crucial role in cancer and D. stramonium has medicinal properties. This study aims to identify the binding mode and key residues of newly isolated phytoconstituents with CDK4.