Simultaneous Ligand and Protein Conformational Change

Modes of protein motion determined by harmonic dynamics or principal component analysis (PCA) serve to describe essential collective motions and they can be introduced directly into the docking procedure. Most conformational variations are captured approximately by a few essential modes. Included as additional variables in protein-ligand docking, they can be optimized and thus the collective protein motions and ligand conformations are simultaneously explored [91-93]. 

An interesting data structure, called flexibility tree, can be employed in the search for the docked complex structure and it allows to combine several flexibility techniques [95]. The data structure hierarchically encodes the flexibility of a protein in variables that allow several protein parts to experience different kinds of moves. Flexibility of domains may be described via normal mode or hinge motions, and side chains are allowed to explore rotameric states. Flexibility trees for protein and ligand are implemented in Flip Dock that provides a genetic algorithm to optimize the variables to gain an induced fit complex ]96]. 

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