Ligand and Protein Conformational Change

A similar geometric approach assigns intrinsic values to grid points to describe the surface, interior, and exterior volumes of the molecules. Shape matches are determined by calculating correlation functions. The correlation values indicate surface match, penetration, or no contact at all [62]. This method is especially successful in protein-protein docking applications and belongs to the standard approaches in this field. 

Soft receptors are an easy and efficient way to model a certain degree of protein flexibility. Their major disadvantage is certainly a substantial lack of accuracy. Usually, soft docking is the initial step of an induced fit workflow before a complex refinement occurs. 

To improve the efficiency of adjusting side chain rotamers, Schaffer and Verkhiv-ker implemented a postdocking side chain optimization procedure using the deadend elimination (DEE) algorithm, follo ved by local minimizations and energy evaluations of all generated DEE solutions [66]. 

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]. 

Approaches That Consecutively Place Ligands and Optimize the Resulting Complex 

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