Supplementary data are available at Bioinformatics online.

Flavonoids can bind Ab 42 to inhibit the aggregation of Ab 42 monomer. However, the inhibitory mechanism remains unknown. Herein, comparable molecular dynamics simulations for a total of 710 ns were performed to study its mechanism. The in silico experiments revealed that flavonoids halt the conformational transition of Ab 42 monomer by inhibiting b-sheet formation; the flavonoids push the residues D23 and K28 of Ab 42 to be exposed to solvated water, destroy the salt bridge between D23 and K28, induce the conformational distribution of Ab 42 into local minimization energy conformational state, and generate U-shaped Ab 42 configurations, which have more stable helixes and fewer unstable random coils. Moreover, simulation results from the free energy landscape and binding free energy analyses suggest that biflavonoids are superior to monoflavonoids in inhibiting conformational transition of Ab 42 monomer. These findings agree with the experimental data and may help in the design of new agents that will inhibit the conformational transition of Ab 42 so as to treat Alzheimer's disease.

Cyclin-dependent kinases (CDKs), a family of mammalian heterodimeric kinases, play central roles in the regulation of cell cycle progression, transcription, neuronal differentiation, and metabolism.