A review of tests for exponentiality with Monte Carlo comparisons.

In this paper, 91 different tests for exponentiality are reviewed. Some of the tests are universally consistent while others are against some special classes of life distributions. Power performances of 40 of these different tests for exponentiality of datasets are compared through extensive Monte Carlo simulations. The comparisons are conducted for different sample sizes of 10, 25, 50 and 100 for different groups of distributions according to the shape of their hazard functions at 5 percent level of significance. Also, the techniques are applied to two real-world datasets and a measure of power is employed for the comparison of the tests. The results show that some tests which are very good under one group of alternative distributions are not so under another group. Also, some tests maintained relatively high power over all the groups of alternative distributions studied while some others maintained poor power performances over all the groups of alternative distributions. Again, the result obtained from real-world datasets agree completely with those of the simulation studies.

Fragment-based virtual screening discovers potential new Plasmodium PI4KIIIß ligands.

Type III beta phosphatidylinositol 4-kinase (PI4KIIIß) is the only clinically validated drug target in Plasmodium kinases and therefore a critical target in developing novel drugs for malaria. Current PI4KIIIß inhibitors have solubility and off-target problems. Here we set out to identify new Plasmodium PI4K ligands that could serve as leads for the development of new antimalarial drugs by building a PPI4K homology model since there was no available three-dimensional structure of PfPI4K and virtually screened a small library of ~ 22 000 fragments against it. Sixteen compounds from the fragment-based virtual screening (FBVS) were selected based on ≤ - 9.0 kcal/mol binding free energy cut-off value. These were subjected to similarity and sub-structure searching after they had passed PAINS screening and the obtained derivatives showed improved binding affinity for PfPI4K (- 10.00 to - 13.80 kcal/mol). Moreover, binding hypothesis of the top-scoring compound (31) was confirmed in a 100 ns molecular dynamics simulation and its binding pose retrieved after the system had converged at about 10 ns into the evolution was described to lay foundation for a rationale chemical-modification to optimize binding to PfPI4K. Overall, compound 31 appears to be a viable starting point for the development of PPI4K inhibitors with antimalarial activity.