Design and Computational Evaluation of Tubulin-Targeting PROTACs for Brain Cancer Therapy

Official repository of the data, scripts and structures employed in and produced during the work presented in "Design and Computational Evaluation of Tubulin-Targeting PROTACs for Brain Cancer Therapy". The content of the repository is organized as follows: Starting ligands databases: Database_colchicine.zip : employed colchicine analogs in mol, pdb, mol2, and moe database format. Database_combretastatin.zip : employed combretastatin derivatives in mol, pdb, and moe database format. Database_ExperimentalStructures.zip : experimental compounds in mol, pdb, mol2, and moe database format. Tubulin homology models: Tubulin_Models_1SA0.zip : fasta sequences, homology models, bound ligands, molecular dynamics input and output files, and clustering results for each of the 8 tubulin dimers considered in the study. Docking: Docking_vina_colchicine.zip : vina config files, compounds pdbqt, and docking results for colchicine analogs dataset. Docking_vina_combretastatin.zip : vina config files, compounds pdbqt, and docking results for combretastatins dataset. [To be uploaded] Docking_vina_exp.zip : vina config files, compounds pdbqt, and docking results for experimental compounds dataset. [To be uploaded] ADMET predictions: ADMET.zip : Simulations Plus' ADMET Predictor results for colchicine analogs, combretastatins, and experimental compounds datasets. MMPBSA: MMPBSA.zip : input and output files for molecular dynamics, clustering, and rmsd of the tubulin dimers containing tubulin beta III and VI, and the UBR1 structure. MMPBSA calculations for tubulin beta III and VI in complex with selected ligands. PROTAC structures: PROTACs.zip : structures of the PROTACs designed from each of the seven most promising tubulin-binding ligands. Data provided in ChemDraw, mol, mol2, and moe database format. PROTAC-mediated ternary structure prediction in MOE: Ternary_Complex_Prediction.zip : moe output files and databases of the PROTAC-mediated ternary complexes, obtained via docking simulations in MOE. [To be uploaded] Ternary_Complex_Prediction_Best.zip : moe databases for the best PROTACs and the most reliable ternary complexes, extracted from the docking data stored in Ternary_Complex_Prediction.zip.