Genetic optimization for ligand docking

Figure 5.26 Virtual screening of a combinatorial amide library LI targeted towards Candida rugosa lipase using Genetic Optimization for Ligand Docking (GOLD).

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]. 

A molecular mechanics optimization allo vs partial to full atom flexibility of the protein through an energy minimization of the protein-ligand complexes and can be used for postprocessing of docked poses. In favor of that, various minimization methods ranging from a steepest descent to a genetic algorithm can be used [67]. 

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