Alexandre Bonvin bio photo

Computational Structural Biology group focusing on dissecting, understanding and predicting biomolecular interactions at the molecular level.

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Advanced refinement of molecular complexes

The HADDOCK2.4 server provides a dedicated web interface to run a refinement on a molecular complex (still experimental). This nice feature is accessible via the Submit File interface of the HADDOCK2.4 portal and requires a registered account with Expert level access.

As input, only a PDB file for each partner of the complex (for a unique PDB file, you need to specify two different chain IDs). You can optionally change the weight of the different energy terms used in the HADDOCK score to assess the quality of your models. A fine-tuned set of parameters will be then used by HADDOCK to perform the water refinement.

However, it is sometimes interesting to tune this default set of parameters to cope with particular cases like unusual histidine protonation states, multibody docking, ensemble and/or cross-docking, etc. To do so, it is possible to use the regular submission interface (needs Guru access level) and change few parameters to only use the refinement capability of HADDOCK:

In the “Distance Restraints” section:

  • Define center of mass restraints to enforce contact between the moleculesTrue
  • Define surface contact restraints to enforce contact between the moleculesTrue

In then “Sampling parameters” section:

  • Number of structures for rigid body docking → Same as the number of models you want HADDOCK to generate in water
  • Number of structures for semi-flexible refinement → Same as the number of models you want HADDOCK to generate in water
  • Sample 180 degrees rotated solutions during rigid body EMFalse
  • Refine with short molecular dynamics in explicit solvent? -> True

In then “Advanced Sampling Parameters” section:

  • Perform cross-dockingFalse
  • Multiply the number of calculated structures by all combinationsTrue
  • Randomize starting orientationsFalse
  • Perform initial rigid body minimisationFalse
  • Allow translation in rigid body minimisationFalse
  • Number of MD steps …*4 → 0 for the 4 values (respectively 500/500/1000/1000 by default)

Those few changes will force HADDOCK to only perform a water refinement as if you would have submitted your run via the refinement interface mentioned above.

It is also possible to perform a similar refinement using the local version and changing the corresponding parameters. An example is also provided in the examples/refine-complexes directory.