Computational Analysis of Natural Compounds as Cyclin-Dependent Kinase-5 Inhibitors for Alzheimer's and Parkinson's Disease

Abstract

Deregulation of cyclin-dependent kinase-5 is a hallmark of different neurodegenerative disorders, including Alzheimer's and Parkinson's disease. Herein, we have screened different natural compounds with anticancer properties against cyclin-dependent kinase-5 enzyme. The blood-brain barrier permeability and pharmacokinetic analysis, including various descriptors, screened 27 natural compounds. The docking of candidate compounds identified 3 compounds with good docking energies and stable interactions when compared to the reference drug roscovitine. Further, molecular dynamics simulation analysis including root mean square deviation, root mean square fluctuation, the radius of gyration and binding energies for 50ns revealed two compounds. Overall, we recommend two natural products apigenin and salvianolic acid as candidate inhibitors to target cyclin-dependent kinase-5 for treating Alzheimer's and Parkinson's disease.