Computational protocol: Borreliacidal activity of Borrelia metal transporter A (BmtA) binding small molecules by manganese transport inhibition

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Protocol publication

[…] The BmtA structure was predicted from its sequence using the I-Tasser program. The final model chosen was that with the highest C-score (confidence score) or confidence score and prepared for Autodock Vina using Autodock tools. Specifically, charges and nonpolar hydrogens were added using default parameters in MGLTools. Autodock Vina 1.0.2 was used for all screenings in this study. The size of the docking grid was expanded from defaults to include the entire BmtA structure. The stringency of docking was set to 8, the default parameter. Compounds used for screening were from the NCI Diversity Set II obtained from NCI and collections of FDA approved compounds obtained from www.drugbank.ca. The NCI Diversity Set II is a collection of around 2,000 compounds that are a part of the full NCI screening collection. Most of the compounds in this library are relatively rigid with five or fewer rotatable bonds allowing for a fast initial round of screening to obtain an initial idea of the types of chemical structures with high affinity for BmtA. In addition, most compounds possess pharmacologically desirable characteristics. They do not belong to class of polycyclic aromatic hydrocarbon, electrophilic, or organometallic molecules. Structural representations of the NCI Diversity in Set II were obtained from the NCI website and converted to a protein data bank (pdb) format. Individual pdb files were prepared for docking using the prepare_ligand.py scripts form MGLTools 1.5.4 using the largest nonbonded fragment present. Structural representations of the FDA approved small molecules were created using Chem3D Pro 12.0, converted into pdb formats, and prepared for docking using the same prepare_ligand.py scripts form MGLTools 1.5.4.The free energies of binding in kcal/mol as produced in Autodock Vina were used to score the ligand affinity with a lower free energy indicating greater affinity of the ligand for the protein. […]

Pipeline specifications

Software tools I-TASSER, AutoDock Vina
Application Protein interaction analysis
Organisms Borreliella burgdorferi
Diseases Borrelia Infections, Infection, Lyme Disease
Chemicals Manganese, Yohimbine, Loratadine