Docking to PTR1 and DHFR targets and off-targets

The New Medicines for Trypanosomatidic Infections - NMTrypI project aimed at obtaining new candidate drugs against Trypanosomatidic infections with appropriate efficiency from the lead phase to the final preclinical phase that are more accessible to patients.

Multidisciplinary development of selective anti-parasitic multi-target inhibitors of PTR1/DHFR based on a pteridine scaffold.

Compound data, library construction schemes and preparation routine for small drug-like molecules as ligands in docking and for further analysis.

Prepared target (parasite PTR1, DHFR) and off-target (human DHFR) protein receptors for docking studies, in part with conserved structural water sets, and the corresponding preparation routine.

Docking results of pteridine-based compounds in different target PTR1 and DHFR receptors and the off-target human DHFR when treating ligands as flexible and the protein receptors as a rigid-body.

Docking results of pteridine-based compounds in different target PTR1 and DHFR receptors and the off-target human DHFR when using an induced fit docking routine with an initial crude ligand placement step, subsequent receptor optimization in response to ligand binding and another docking step into the optimized receptor.

Zip-archive with results for reference and all designed pteridines in their neutral and N1-protonated variant as multi-model PDB files, ordered as ranked by Glide docking scores, in the TbPTR1 receptor based on PDB-ID 2x9g without explicit water molecules. Docking results obtained by rigid-body XP docking with Schrödinger Glide (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Glide v6.9). For further details and naming conventions also refer to the README file.

Zip-archive with results for reference and all designed pteridines in their neutral and N1-protonated variant as multi-model PDB files, ordered as ranked by Glide docking scores, in the TbPTR1 receptor based on PDB-ID 2x9g with explicit conserved structural water molecules. Docking results obtained by rigid-body XP docking with Schrödinger Glide (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Glide v6.9). For further details and naming conventions also refer to the README file. ...

Zip-archive with results for reference and all designed pteridines in their neutral and N1-protonated variant as multi-model PDB files, ordered as ranked by Glide docking scores, in the TbDHFR receptor based on PDB-ID 3rg9 without explicit water molecules. Docking results obtained by rigid-body XP docking with Schrödinger Glide (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Glide v6.9). For further details and naming conventions also refer to the README file.

Zip-archive with results for reference and all designed pteridines in their neutral and N1-protonated variant as multi-model PDB files, ordered as ranked by Glide docking scores, in the LmPTR1 receptor based on PDB-ID 1e92 without explicit water molecules. Docking results obtained by rigid-body XP docking with Schrödinger Glide (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Glide v6.9). For further details and naming conventions also refer to the README file.

Zip-archive with results for reference and all designed pteridines in their neutral and N1-protonated variant as multi-model PDB files, ordered as ranked by Glide docking scores, in the LmPTR1 receptor based on PDB-ID 1e92 with explicit conserved structural water molecules. Docking results obtained by rigid-body XP docking with Schrödinger Glide (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Glide v6.9). For further details and naming conventions also refer to the README file. ...

Zip-archive with results for reference and all designed pteridines in their neutral and N1-protonated variant as multi-model PDB files, ordered as ranked by Glide docking scores, in the LmDHFR receptor based on the published homology model of LmDHFR (Panecka-Hofman et al. (2017) Biochim Biophys Acta Gen Subj. 1861(12), 3215-3230. DOI: 10.1016/j.bbagen.2017.09.012) without explicit water molecules. Docking results obtained by rigid-body XP docking with Schrödinger Glide (Schrödinger, LLC, New York, ...

Zip-archive with results for reference and all designed pteridines in their neutral and N1-protonated variant as multi-model PDB files, ordered as ranked by Glide docking scores, in the hDHFR receptor based on PDB-ID 1u72 without explicit water molecules. Docking results obtained by rigid-body XP docking with Schrödinger Glide (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Glide v6.9). For further details and naming conventions also refer to the README file.

Zip-archive with results for reference and all designed pteridines in their neutral and N1-protonated variant as multi-model PDB files, ordered as ranked by Glide docking scores, in the hDHFR receptor based on PDB-ID 1u72 with explicit conserved structural water molecules. Docking results obtained by rigid-body XP docking with Schrödinger Glide (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Glide v6.9). For further details and naming conventions also refer to the README file. ...

Zip-archive with induced fit docking results for reference compounds methotrexate and 1b as well as the N10-modified compounds 2a and 2e in their neutral and N1-protonated variants and the PABA-modified compound 3d in neutral form as individual ligand:receptor complex PDB files. The files are ordered as ranked by Glide docking scores. The TbPTR1 receptor was based on PDB-ID 2x9g without additional water molecules. Docking results were obtained by Induced Fit docking with Schrödinger Glide and ...

Zip-archive with induced fit docking results for reference compounds methotrexate and 1b as well as the N10-modified compounds 2a and 2e in their neutral and N1-protonated variants and the N10-modified compound 2c and merged-series compound 5e in neutral form as individual ligand:receptor complex PDB files. The files are ordered as ranked by Glide docking scores. The TbPTR1 receptor was based on PDB-ID 2x9g with explicit conserved structural water molecules. Docking results were obtained by Induced ...

Zip-archive with induced fit docking results for methotrexate in its neutral and N1-protonated variant as individual ligand:receptor complex PDB files. The files are ordered as ranked by Glide docking scores. The TbDHFR receptor was based on PDB-ID 3rg9 without additional water molecules. Docking results were obtained by Induced Fit docking with Schrödinger Glide and Prime in the Induced Fit docking workflow (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Induced Fit Docking ...

Zip-archive with induced fit docking results for reference compounds methotrexate, 1b and 1c as well as the N10-modified compound 2e in their neutral and N1-protonated variants and the N10-modified compound 2a and Tail-modified compounds 4e, 4f, 4i and 4j in neutral form as individual ligand:receptor complex PDB files. The files are ordered as ranked by Glide docking scores. The LmPTR1 receptor was based on PDB-ID 1e92 without additional water molecules. Docking results were obtained by Induced ...

Zip-archive with induced fit docking results for reference compounds methotrexate, 1b and 1c as well as the N10-modified compound 2e in their neutral and N1-protonated variants and the PABA-modified compound 3e in neutral form as individual ligand:receptor complex PDB files. The files are ordered as ranked by Glide docking scores. The LmPTR1 receptor was based on PDB-ID 1e92 with explicit conserved structural water molecules. Docking results were obtained by Induced Fit docking with Schrödinger ...

Zip-archive with induced fit docking results for methotrexate in its neutral and N1-protonated variant as individual ligand:receptor complex PDB files. The files are ordered as ranked by Glide docking scores. The LmDHFR receptor was based on a published homology model of LmDHFR (Panecka-Hofman et al. (2017) Biochim Biophys Acta Gen Subj. 1861(12), 3215-3230. DOI: 10.1016/j.bbagen.2017.09.012) without additional water molecules. Docking results were obtained by Induced Fit docking with Schrödinger ...

Zip-archive with induced fit docking results for methotrexate in its neutral and N1-protonated variant as individual ligand:receptor complex PDB files. The files are ordered as ranked by Glide docking scores. The hDHFR receptor was based on PDB-ID 1u72 without additional water molecules. Docking results were obtained by Induced Fit docking with Schrödinger Glide and Prime in the Induced Fit docking workflow (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Induced Fit Docking ...

Zip-archive with induced fit docking results for methotrexate in its neutral and N1-protonated variant as individual ligand:receptor complex PDB files. The files are ordered as ranked by Glide docking scores. The hDHFR receptor was based on PDB-ID 1u72 with explicit conserved structural water molecules. Docking results were obtained by Induced Fit docking with Schrödinger Glide and Prime in the Induced Fit docking workflow (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Induced ...

Compound SMILES of resynthesized or newly designed pteridine compounds 1b, 1c, 2a-e, 3a-e, 4a-j and 5a-f used for ligand preparation within Maestro (Schrödinger, LLC, New York, NY, Schrödinger Release 2015-4, 2015, Maestro.). SMILES strings and compound identifiers are comma-separated and can be readily imported in Maestro.

Zip archive of N1 protonated reference and newly synthesized pteridines (series 1-5) in SDF format.

PDB file of the prepared human dihydrofolate reductase docking receptor based on chain A of PDB-ID 1u72 with a conserved set of structural waters.

PDB file of the prepared human dihydrofolate reductase docking receptor based on chain A of PDB-ID 1u72 without additional water molecules.

This SOP describes the preparation of pteridine ligand 3D structures from SMILES or other input formats with the LigPrep routine as embedded in Schrödinger Maestro for usage in docking runs and in silico ADME-Tox property prediction.

This SOP describes the docking receptor preparation of PTR1 and DHFR receptor PDB files, performed with the Maestro Protein PrepWizard and the Glide grid generation routine. The optional identification and integration of conserved structural water molecules with the WatCH tool is also covered.

This SOP describes the docking of pteridine libraries into PTR1 or DHFR target receptors, using Glide in Schrödinger Maestro with the XP (eXtra Precision) protocol.

This SOP describes the docking of pteridine libraries into PTR1 or DHFR target receptors, using Glide and Prime in Schrödinger Maestro as part of the Induced Fit workflow to allow for receptor side chain reorganization upon ligand binding.