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_1SA0.zip : config files, compounds pdb and pdbqt, and docking results for all the ligands dataset used, for both AutoDock and MOE.

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.

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.

本仓库为论文《靶向微管蛋白的蛋白降解靶向嵌合体（PROTACs）用于脑癌治疗的设计与计算评价》中所使用及产出的数据、脚本与结构的官方开源仓库。

本仓库内容组织如下：

起始配体数据库：

Database_colchicine.zip：包含本研究使用的秋水仙碱类似物，数据格式涵盖mol、pdb、mol2及moe数据库格式。
Database_combretastatin.zip：包含本研究使用的康普瑞汀衍生物，数据格式涵盖mol、pdb及moe数据库格式。
Database_ExperimentalStructures.zip：包含实验化合物，数据格式涵盖mol、pdb、mol2及moe数据库格式。

微管蛋白同源建模模型：

Tubulin_Models_1SA0.zip：包含本研究中涉及的8种微管蛋白二聚体的fasta序列、同源建模模型、结合配体、分子动力学输入与输出文件，以及聚类结果。

分子对接：

Docking_vina_colchicine.zip：包含秋水仙碱类似物数据集的AutoDock Vina配置文件、化合物pdbqt文件及对接结果。
Docking_1SA0.zip：包含本研究使用的全部配体数据集的配置文件、化合物pdb及pdbqt文件，以及AutoDock与分子操作环境（MOE）下的对接结果。

ADMET预测：

ADMET.zip：包含Simulations Plus公司的ADMET Predictor软件对秋水仙碱类似物、康普瑞汀及实验化合物数据集的预测结果。

MMPBSA计算：

MMPBSA.zip：包含针对含βⅢ型和βⅥ型微管蛋白的微管蛋白二聚体以及UBR1结构的分子动力学、聚类及均方根偏差（RMSD）相关的输入与输出文件；同时包含βⅢ型和βⅥ型微管蛋白与选定配体形成复合物后的MMPBSA计算结果。

PROTAC结构：

PROTACs.zip：包含从7种最具潜力的微管蛋白结合配体设计得到的PROTACs结构，数据格式涵盖ChemDraw、mol、mol2及moe数据库格式。

MOE环境下PROTAC介导的三元结构预测：

Ternary_Complex_Prediction.zip：包含通过MOE对接模拟得到的PROTAC介导的三元复合物的MOE输出文件及数据库。
Ternary_Complex_Prediction_Best.zip：包含从Ternary_Complex_Prediction.zip的对接数据中提取的最优PROTACs及最可靠三元复合物的MOE数据库。