Journal
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Volume 40, Issue 6, Pages 2815-2827Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2020.1844050
Keywords
Alzheimer’ s disease; neurofibrillary tangles; CDK5; virtual screening; molecular docking; molecular dynamics simulation; principal component analysis; MM-PBSA
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Funding
- ICMR [ISRM/11(53)/2019]
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Alzheimer's disease (AD) is a complex global disease characterized by amyloid beta and neurofibrillary tangles. This study screened compounds against CDK5 and identified two potential lead compounds through pharmacokinetics analysis.
Alzheimer's disease (AD) is a multifactorial complex and wide spreading global disease. It is a chronic neurodegenerative disorder characterized by amyloid beta (A beta) and neurofibrillary tangles (NFTs). Several enzymes are involved in which CDK5 is a major tau phosphorylation enzyme. We have screened (n = 5,36,801) compounds against CDK5 and 392 compounds were selected for pharmacokinetics analysis. In the pharmacokinetics analysis, various descriptors were used for filtering the compounds. After that 16 compounds with the control compound Z3R were employed for the redocking using Autodock Vina and Autodock. Lastly, four compounds were selected and employed for 100 ns MDS studies. On the basis of various MD analysis like RMSD, RMSF, Rg, SASA, Number of hydrogen bonds, Principal component analysis and binding free energy (CDK5-ZINC6261568: -129.50 kJ.mol(-1) and CDK5-ZINC14168360: -191.16 kJ.mol(-1)), we have found that ZINC6261568 and ZINC14168360 can act as a lead compound against the CDK5. Communicated by Ramaswamy H. Sarma
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