A Structure-Based Pipeline for Targeting the Long Non-Coding RNA MALAT1

Data for molecular dynamics (MD) simulations and molecular docking calculations on the triple-helix structure of the MALAT1 RNA. The input_output_MDsimulations.zip file contains input files to perform both plain (i.e. unbiased) and Hamiltonian replica-exchange (hREX) MD simulations of the RNA, as well as the corresponding output trajectories. The malat1_analyses.tar.gz file contains all RNA and ligand structures for docking via AutoDock-GPU and rDock, as well as output data to perform analysis of results. The Notebook_malat1.ipynb Jupyter Notebook illustrates how to perform all the analyses, and can also be straightforwardly consulted at https://github.com/CompMedChemLab/project_malat1; the notebook should be run under the malat1 conda environment, which can be installed using the environment.yml file. A tree.txt file is provided to help navigating the five main subfolders: - The folder pocketron_malat1/ contains all outputs produced by Pocketron, including the pocket–residue matrices, the communication-network files, and all intermediate data generated for the analysis- The folder data_trj/ stores MD trajectories and the corresponding reference PDB structures used for the analyses reported in the notebook. It contains both the unbiased and HREX simulations for RMSD/eRMSD calculations, PCA and centroid extraction- The folder data_docking/ contains all docking-related materials, organized into: i) input files, divided into AutoDock and rDock inputs, together with the original conformations extracted from the MD ensemble for both binding sites; ii) site-specific directories (site1/ and site2/), containing complete results for every ligand across all conformations, with separate subfolders for AutoDock-GPU and rDock outputs that include rescoring results obtained using multiple scoring functions, and PCA directories storing the data for the principal component analyses performed on the docking results for each site- The folder data_fingernat/ contains all FingeRNAt interaction-fingerprint results for both binding sites. For each site, three subfolders provide: i) the global FingeRNAt results for all poses, ii) clustering results, and iii) FingeRNAt results computed only for the selected clusters retained for PCA and regression analyses- The folder data_plots/ stores all variables and data structures saved in pickle binary format during the notebook-based analyses The MD_docking_poses.zip file contains the input subfolder with all necessary files to perform the plain MD simulations of the docking poses for three representative ligands (P9, P0, O5) in two ionic conditions, while the corresponding output trajectories can be found in the output subfolder. The Python script plot_RMSD_SI.py can be used to generate RMSD plots of the ligands after optimal alignment to residues in Site 2 of the RNA. The complexes obtained from docking for the other ligands are also provided in the docking_complexes_site2_cluster3 subfolder.