In silico Screening and Evaluation of Plasmodium falciparum Protein Kinase 5 (PK5) Inhibitors.

ABSTRACT: An in silico screen of 350 000 commercially available compounds was conducted with an unbiased approach to identify potential malaria inhibitors that bind to the Plasmodium falciparum protein kinase 5 (PfPK5) ATP-binding site. PfPK5 is a cyclin-dependent kinase-like protein with high sequence similarity to human cyclin-dependent kinase 2 (HsCDK2), but its precise role in cell-cycle regulation remains unclear. After two-dimensional fingerprinting of the top scoring compounds, 182 candidates were prioritized for biochemical testing based on their structural diversity. Evaluation of these compounds demonstrated that 135 bound to PfPK5 to a similar degree or better than known PfPK5 inhibitors, confirming that the library was enriched with PfPK5-binding compounds. A previously reported triazolo

SUBMITTER: Eubanks AL 

PROVIDER: S-EPMC6436633 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature