· Delarue web servers
· Nomad Flow-chart
· Normal Mode calculation
  · Examples (Movies)
  · Submit a job (from PDB file)
  · Split trajectory (for MR)
  · Generate decoys (MixMod)
  · Elastic Energy (Perturb. Anal.)
· Overlap coefficients
  · Submit a job
  · Include Profit step
· X-Ray refinement
  · Standard refinement
  · Screening Mol. Repl. Solns.
· EM refinement
  · Documents/Examples
  · Get Structure Factors
  · Submit a job (no NCS)
  · Submit job with NCS
· Docking refinement
  · Submit a job (refinement)
  · Submit a job (scanning)
· Force field methods
  · Energy minimization
  · Gromacs NMA
· References
· Homes/Links
· Job queue status

Docking refinement

This server uses normal mode analysis to refine one of the molecules in a pair of docked structures. A common case is receptors docked with (small) rigid ligands, where it essentially tries to predict the induced fit flexibility (see classical examples).

As input, you need to provide the flexible and fixed structures as PDB files, with the structures at least approximately docked. This method does not yet attempt the molecular recognition part of docking, so you might want to employ a separate docking program first.

Feedback is always welcome; the method is described in detail in an recent paper.

The refinement is performed by first determining the lowest-frequency all-atom normal modes of the flexible structure, and then using these modes as the degrees of freedom in optimization. Normally about 5 should be enough; if too few are included there aren't enough degrees of freedom, and if too many are included the optimization won't be efficient since the available space is too large. Trial and error might be a good idea!

The actual entity that is minimized is the nonbonded Lennard-Jones and Coulomb energy cross-terms between the structures, using soft-core potentials to avoid problems with overlapping atoms. The optimization can either be performed by scanning normal mode amplitudes (recommended), or by using a quasi-Newtonian minimizer with the amplitudes as degrees of freedom. To avoid run-away issues we strongly recommend that you apply restraints to the mode amplitudes. The output will be a new PDB structure of the flexible, which hopefully is a better fit for the fixed one.




  Marc Delarue http://lorentz.dynstr.pasteur.fr
Page last modified 18:06 January 24, 2006.