Computational protocol: Defining the Schistosoma haematobium kinome enables the prediction of essential kinases as anti-schistosome drug targets

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Protocol publication

[…] To assess the druggability of individual predicted kinases and to prioritise them as potential targets in S. haematobium, essentiality was inferred by selecting S. haematobium proteins homologous (BLASTP; e-value ≤10−5) to C. elegans, D. melanogaster and/or M. musculus kinases with a lethal phenotype upon gene perturbation - listed in WormBase, FlyBase and MGI. Essential kinases were considered to represent metabolic chokepoints if only one gene was assigned to one KEGG orthologous gene (KO) term for a KEGG pathway. These kinases were then matched to homologous kinase sequences in the databases Kinase SARfari and DrugBank v.3.0 (ref. ) using PSI-BLAST v.2.2.26+ employing an e-value cut-off of 10−30 (ref. ). If both query and target sequence had the same kinase classification (using Kinannote), the sequence in the database had one or more ligands that met the Lipinski rule-of-five and was flagged as “medicinal chemistry friendly”, salient information on associated ligands (chemicals or small molecules) was extracted from the two databases and used to assess the druggability of the target. Prioritised kinases predicted to bind compounds approved by the FDA for use in humans or assessed in clinical trials, as indicated in Kinase SARfari (https://www.ebi.ac.uk/chembl/sarfari/kinasesarfari), were considered to have potential as drug targets. Kinases with entries in DrugBank were prioritised as drug targets if at least one associated small molecule (with a description of its properties) was found in this database. […]

Pipeline specifications

Software tools BLASTP, Kinannote
Databases FlyBase WormBase ChEMBL DrugBank KEGG Kinase SARfari KEGG PATHWAY
Application Protein sequence analysis
Organisms Schistosoma haematobium, Homo sapiens, Spirometra erinaceieuropaei
Diseases Schistosomiasis, Schistosomiasis haematobia
Chemicals Praziquantel