Enhanced-sampling MD simulations of the RAD51-BRC4 complex

Molecular dynamics simulations of the RAD51-BRC4 complex, using enhanced sampling methods (steered MD and metadynamics). The simulations integrate experimental information, namely SAXS (in the steered MD) and XL-MS (in the metad). All input files necessary to perform the simulations are provided, including the initial model of the full RAD51-BRC4 complex generated via AlfaFold2 after proper equilibration, used to start the steered MD, as well as the output files (including MD trajectories). In the notebook folder, we also provide a Jupyter Notebook to analyze results and perform ensemble reweighting through the maximum entropy principle; the folder also gathers all files necessary to run the notebook and a lighter version of the trajectories.

The entire output trajectory from the metad simulation, which together with the frame-by-frame weights determined via maxent represents the reweighted ensemble, can be found in the /metad/output subfolder in .xtc format. The structures can also be directly accessed in PDB format in the /reweighted_ensemble_pdb folder, each labelled with the corresponding weight in the REMARK header line. The frame-by-frame weights associated with the reconstructed conformational ensemble can be found in portable formats (both binary and human-readable) in the /notebook/output_check subfolder; the weights can also be easily recomputed and saved using dedicated instructions in the notebook. In the notebook/output_check/out_cluster_analysis subfolder we also supply representative structures, i.e. cluster centroids, for highest-weighted clusters from the reweighted ensemble in the form of individual PDBs, labelled with the corresponding cluster weight in the REMARK header line of each PDB; instructions to identify and save these structure files can also be found in the notebook.

The notebook can also be easily consulted at https://github.com/CompMedChemLab/project_saxs-xlms-md_rad