HADDOCK: an information-driven flexible docking approach

Alexandre M. J. J. Bonvin, Utrecht University.
 

    In my talk, I will describe our recently developed information-driven flexible docking approach HADDOCK (High Ambiguity Driven protein protein DOCKing) (http://www.nmr.chem.uu.nl/haddock), that makes use of biochemical and/or biophysical information. The experimental information is introduced as highly ambiguous interaction restraints (AIRs) to drive the docking process.
    HADDOCK uses an all-atom representation of the system. Flexibility is accounted for in different ways during the docking protocol:
i) in the initial rigid body energy minimization stage by starting the docking from ensembles of conformations (e.g. a NMR ensemble of structures, snapshots from a MD simulation)
ii) during the semi-flexible simulated annealing refinement stage by allowing flexibility at the interface first, only for side-chain atoms, and then, for both side-chain and backbone atoms
iii) in the final SA refinement in explicit water by progressively allowing flexibility in the remaining of the system in addition to the defined, flexible interface.

Reference:
- Dominguez, C. Boelens, R. and Bonvin, A.M.J.J. (2003). J. Am. Chem. Soc. 113. 1731