Biologically Active Ligands for Yersinia Outer Protein H (YopH): Feature Based Pharmacophore Screening, Docking and Molecular Dynamics Studies
Thangaraju Tamilvanan and Waheeta Hopper
Affiliation: Department of Bioinformatics, School of Bioengineering, Faculty of Engineering & Technology, SRM University, Kattankulathur-603203, Tamil Nadu, India.
Yersinia pestis, a Gram negative bacillus, spreads via lymphatic to lymph nodes and to all organs through the
bloodstream, causing plague. Yersinia outer protein H (YopH) is one of the important effector proteins, which paralyzes
lymphocytes and macrophages by dephosphorylating critical tyrosine kinases and signal transduction molecules. The
purpose of the study is to generate a three-dimensional (3D) pharmacophore model by using diverse sets of YopH
inhibitors, which would be useful for designing of potential antitoxin. In this study, we have selected 60 biologically
active inhibitors of YopH to perform Ligand based pharmacophore study to elucidate the important structural features
responsible for biological activity. Pharmacophore model demonstrated the importance of two acceptors, one hydrophobic
and two aromatic features toward the biological activity. Based on these features, different databases were screened to
identify novel compounds and these ligands were subjected for docking, ADME properties and Binding energy prediction.
Post docking validation was performed using molecular dynamics simulation for selected ligands to calculate the Root
Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF). The ligands, ASN03270114, Mol_252138,
Mol_31073 and ZINC04237078 may act as inhibitors against YopH of Y. pestis.
Keywords: Induced fit docking, MM-GBSA, molecular dynamics, pharmacophore, Yersinia pestis, YopH.
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