Computational Analysis of Apicomplexan Kinomes

Abstract

Apicomplexan parasites are responsible for a large number of diseases affecting much of the World's population, and as a result place a tremendous burden on the economic development of many countries. Protein kinases, a large family of enzymes regulating almost every known cellular process, have emerged as potential key drug targets for antiparasitic therapies. In this chapter we review recent bioinformatic investigations aimed at identifying the most promising protein kinase drug targets. An overview of the resources available for the study of apicomplexan genomes is first provided, especially databases of protein kinases and custom methods for the sequence analysis of kinases, as well as some practical guidelines for the annotation of protozoan kinomes. Finally, recent findings on apicomplexan kinomes obtained from comparative studies of multiple species are summarized, and an explanation is provided as to how heterogeneous datasets (functional genetic, expression, phylogenetic and structural data) are integrated not only to identify the most important protein kinase drug targets but also to find their Achilles' heels in order to achieve their selective targeting.