Ligand-protein Docking techniques

Molecular Docking is a versatile tool in structure based drug design. This technique is able to predict possible orientations of one molecule to another. In this section we will focus on protein-ligand docking, describing the interaction of a small molecule in a binding pocket of the protein of interest. 

Protein-based methods rely upon the structural information extracted from the X-ray crystallographic and/or homology protein structures. These also include docking techniques for the exploration of possible binding modes of a ligand to a given transporter protein. 

Virtual screening applications based on superposition or docking usually contain difficult-to-solve optimization problems with a mixed combinatorial and numerical flavor. The combinatorial aspect results from discrete models of conformational flexibility and molecular interactions. The numerical aspect results from describing the relative orientation of two objects, either two superimposed molecules or a ligand with respect to a protein in docking calculations. Problems of this kind are in most cases hard to solve optimally with reasonable compute resources. Sometimes, the combinatorial and the numerical part of such a problem can be separated and independently solved. For example, several virtual screening tools enumerate the conformational space of a molecule in order to address a major combinatorial part of the problem independently (see for example [199]). Alternatively, heuristic search techniques are used to tackle the problem as a whole. Some of them will be covered in this section. 

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