HADDOCK

Training material used during the "EMBO practical course on Practical Integrative Structural Biology" event

Training material for the "INSTRUCT training course: Advanced methods for the integration of diverse structural data, Florence IT"

On this page, you can find the links to the HADDOCK and metadynamics (using Gromacs) tutorials given during the BioExcel Summer School on Biomolecular Simulations 2019 in Pula, Italy.

The first tutorial demonstrates the use of cross-linking data from mass spectrometry to guide protein-protein docking in HADDOCK.

The second tutorial illustrates how metadynamics can be used to sample conformations of a binding pocket; those are subsequently used for docking a ligand using HADDOCK. The conformational sampling approach is following the EDES approach described in the following publication:

• A. Basciu, G. Malloci, F. Pietrucci, A.M.J.J. Bonvin and A.V. Vargiu. Holo-like and druggable protein conformations from enhanced-sampling of binding pocket shape. J. Chem. Inf. and Mod. 59, 1515-1528 (2019).

This tutorial will demonstrate the use of HADDOCK for predicting the structure of a protein-protein complex from NMR chemical shift perturbation (CSP) data. Namely, we will dock two E. coli proteins involved in glucose transport: the glucose-specific enzyme IIA (E2A) and the histidine-containing phosphocarrier protein (HPr).

The structures in the free form have been determined using X-ray crystallography (E2A) (PDB ID 1F3G) and NMR spectroscopy (HPr) (PDB ID 1HDN). The structure of the native complex has also been determined with NMR (PDB ID 1GGR).

These NMR experiments have also provided us with an array of data on the interaction itself (chemical shift perturbations, intermolecular NOEs, residual dipolar couplings, and simulated diffusion anisotropy data), which will be useful for the docking. For this tutorial, we will only make use of inteface residues identified from NMR chemical shift perturbation data as described in Wang et al, EMBO J (2000).