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Objective To develop new leads with high activity and specificity for the clinical treatment of Toxoplasmosis,the newly discovered virulence determinant Rop18 was used to be the target for kinase inhibitors virtual screening among the self-built database.Method The crystal structure of Rop18 kinase domain(PDB ID: 4JRN)was downloaded and modified by a Molecular Operating Environment(MOE)software.A set of 46741 published kinase inhibitors 2D structure were downloaded from ChEMBLdb database and searched their preferred conformation by conformational import,then transformed them into the 3D format.Suitable inhibitor binding pocket was selected by analysis of amino acids and surface electric potential in the interaction surface.Ligand-based pharmacophore modeling was used to identify the chemical features responsible for inhibiting ATP-binding pocket of Rop18,and the final model was used to screen the self-built database.Hit compounds were subjected to molecular docking by MOE software,the interaction models of inhibitor and Rop1 8 were established for selection analysis.Results The ATP-binding pocket was selected as the target for inhibitor binding.The final pharmacophore consisted of three hydrogen bond acceptors(HBA),a hydrogen-bond donor(HBD),a hydrophobic feature,a ring aromatic feature,a cation group feature and three excluded volumes.134 hit compounds were revealed in the self-built kinase inhibitor database.After docking into the ATP-binding site,7 drug-like hits were selected as representative leads.Conclusion A high quantitative pharmacophore targeted ATP-binding pocket was constructed based on the crystal structure of Rop18,7 known kinase inhibitors were selected and provides the representative molecular conformation for developing new anti-toxoplasmosis leads.