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 (CROSBI ID 288390)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Gurushankar, Krishnamurti ; Rimac, Hrvoje ; Potemkin, Vladimir ; Grishina, Maria
engleski
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, anti-inflammatory, 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.
D. stramonium ; D. metel L ; Baimantuoluoamide A ; Baimantuoluoamide B ; ChemoSophia ; CDK4 ; MM/GBSA ; 3D/4D QSAR ; Molecular Dynamics ; Molecular Docking
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Podaci o izdanju
1230
2021.
129925
8
objavljeno
0022-2860
1872-8014
10.1016/j.molstruc.2021.129925
Povezanost rada
Farmacija, Interdisciplinarne prirodne znanosti, Kemija