Molecular dynamics input files and analysis data for WRN WT, F730V and F730L complexes with VVD-214

This dataset contains molecular dynamics (MD) input files, representative structures and processed analysis data for WRN helicase domain complexes with VVD-214 in three protein backgrounds: WT, F730V and F730L. These data support the MD-based structural analyses reported in the manuscript “Functional orthogonality of WRN inhibitor resistance enables alternating therapy and mutation-tolerant inhibitor design in MSI-H cancers”.

The deposited files include two compressed archives: Input_files.zip and Analysis data.zip. Input_files.zip contains the GROMACS input files for the WRN WT–VVD-214, WRN F730V–VVD-214 and WRN F730L–VVD-214 systems, including starting structures, topology files, index files, molecular dynamics parameter files and force-field-related files. The systems were prepared for GROMACS simulations using CHARMM36-based topology files, CGenFF ligand parameters, TIP3P water and NaCl ions.

Analysis data.zip contains processed source data used for the MD analyses, including ligand RMSD, protein RMSD, protein RMSF, radius of gyration and the distance between Cys727 and the acrylamide warhead of VVD-214. Representative structures for the WT, F730V and F730L systems are also provided in PDB format. These files enable reproduction and inspection of the key MD-derived analyses used to compare protein conformational dynamics, ligand stability and covalent-warhead positioning across the WT, F730V and F730L WRN backgrounds.

The deposited data include the MD input files, representative structures and processed analysis data required to inspect and reproduce the key MD-derived results reported in the manuscript.