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. 2020 Nov 15;9(11):812. doi: 10.3390/antibiotics9110812

Table 1.

Tools and procedures applicable to the in silico/computational antifungal drug repurposing.

Pathogens
Steps		 Paracoccidioides Species Candida albicans Candida, Aspergillus, and Trychophyton Species Pythium insidiosum Paracoccidioides Species Candida auris
Mining and compilation of pathogen genome data Broad Institute Fungal Genomics Database (https://www.broadinstitute.org/fungal-genome-initiative) The Basic Local Alignment Search Tool (BLASTP), National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/BLAST/);
CLUSTALW, European
Bioinformatics Institute (http://www.ebi.ac.uk/Tools/msa/)		 MOE 2014.09 (PDB search module);
Clustal Omega tool, UniProt server (http://www.ebi.ac.uk/Tools/msa/clustalo/)		 UniProt database (https://www.uniprot.org);
Protein Data Bank (https://www.rcsb.org);
BLASTP (blast 2.2.28_ program) (https://www.ncbi.nlm.nih.gov)		 - -
Identification of orthologs in pathogen isolates OrthoVenn server - - - - -
Identification of homologs in the drug–target databases DrugBank; Therapeutic targets database (TTD) - - - MDL Drug Data Report (MDDR) (BIOVIA and Thomson Reuters);
DrugBank (https://www.drugbank.ca/);
TargetMol provider (http://targetmol.com/)		 -
Selection of essential targets in the Saccharomyces cerevisiae system Database of Essential Genes (DEG) - - - - -
Homology modeling SWISS-MODEL server;
Protein Data Bank
(PDB);
KoBaMIN server;
HCC server; MolProbity		 SWISS-MODEL server;
Ramachandran plot, SAVES
(http://services.mbi.ucla.edu/PROCHECK)		 AMBER99 (with S. cerevisiae chorismate mutase; PDB entry code 4CSM) as a template PubChem server (http://pubchem.ncbi.nlm.nih.gov/) (3D structure);
PreADMET server (https://preadmet.bmdrc.kr/introduction/) (3D structure)		 Homology modeling for Candida albicans thioredoxin reductase [174] Cytochrome P450 51 (CYP51) modeling [175]
Ligand preparation and Molecular docking OMEGA v.3.0.0.1 software by OpenEye Scientific [176];
QUACPAC v.1.7.0.2 software by OpenEye Scientific [177];
OEDocking suite v.3.2.0 by OpenEye Scientific [178];
FRED program with the ChemGauss4 score function in the OEDocking suite		 Protein Preparation Wizard of Schrodinger’s suite 8.5 (Chimeric 1EA1);
Docking between internal ligand (fluconazole) and 1EA1 in Schrodinger’s suite 8.5;
GROMACS 5.0 for molecular dynamics simulations with
GROMOS9643a1 force field;
LIGPREP and
MAESTRO (fluvastatin 3D
structure);
MATLAB version R2015b (plotting and calculations);
Dundee Prodrug 2.5;
GLIDE 5.0		 MOE 2014.09 (Chemical
Computing Group Inc., Sherbooke St, Montreal, QC, Canada) software;
Leadit 2.1.2 (BioSolveIT GmbH, Germany) software;
Gromacs 4.5.5 (Molecular dynamics);
PRODRG2 and GROMOS 53A6 force field (Topology);
Particle Mesh Ewald (PME) method and linear constraint solver (LINCS);
Xmgrace and VMD software		 AutoDock Vina program; PyRx suite open-source software version 0.9.7;
AutoDock Vina program;
Discovery Studio Visualizer version 17.2.0 (Dassault Systemes Biovia Corp.)		 Scaffold Hunter program (http://scaffoldhunter.sourceforge.net/) (selection of top ten best compounds from each database);
GOLD software (docking simulation against Candida albicans thioredoxin reductase);
CORINA (three-dimensional models);
Visual Molecular Dynamics (VMD) program (http://www.ks.uiuc.edu/Research/vmd/);
LigPlot program (https://www.ebi.ac.uk/thornton-srv/software/LIGPLOT/)		 Protein preparation wizard (C. albicans CYP51);
LigPrep module of the Schrodinger suite (sertraline);
Schrodinger suite (LLC, New York, NY) (induced fit molecular docking analysis);
Glide module (extra precision feature for sertraline)
Experimental validation in the target pathogen Modified Clinical and Laboratory Standards Institute (CLSI) protocol Microtiter bioassay 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) microdilution assay Agar- and broth-based assay CLSI M27-A3 [171]
 Microdilution (killing kinetics)
References [15,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192] [18,193,194,195] [16,196,197,198,199,200,201,202,203,204] [17,205,206] [20,171,174,207,208,209,210] [21,175]