Docking (molecular)

Molecular Docking ( short docking, dt: coupling, fitting ) is a bioinformatic / chemo informatics matic method by which the binding mode and, ideally, the binding energy of two adjacent binding biomolecules is predicted. Docking is typically used in the molecular biological and pharmaceutical research. One major area of ​​application is the search for drug candidates for a pharmaceutically relevant problem. Using docking methods large quantities of material can be tested for binding to virtually a target molecule. These in silico binding studies are significantly faster and less expensive than comparable procedures in the wet lab, but as a rule of noticeably lower accuracy.

The prediction takes place on the basis of already known chemical and spatial structure of the two starting molecules. The structure and the liberated energy of binding of the complex formed from the two molecules is not known, prior to the calculation. As a solution, we obtain the best possible approximation to the complex structure and depending on the method and an estimate of the binding energy of the complex.

The molecules involved are highly complex, as a rule, so an a priori calculation of the bound state is not possible at present because of the need for enormous computing capacity. Therefore, all relevant algorithms use strong to very strong approximations of the underlying physics and chemistry to calculate a good estimate of the binding mode.

There are different approaches in order to keep the complexity of the problem in check. The simplest structural approach is the rigid docking, which is based on the simplifying assumption that does not change the molecules involved during the binding process spatially. Furthermore, there are approaches that hold one of the binding partners rigid, while the second ( semi-) is modeled flexibly. The latter is often found in the ligand docking application where small drug-like molecules are considered, their relatively low spatial complexity makes a flexible viewing manageable.

Since they are three-dimensional objects, the mutual positioning and orientation of the molecules in the bound state, ie in a state of lowest energy of interest. In addition, the molecules can learn the process changes in their conformation itself. Although the parameters of this unknown final state could also be determined experimentally, but this is too costly; Therefore, computational methods are used to calculate the virtual space of the complex biochemical and thereby come close to real conditions as possible.

Docking is divided according to the type of the binding partners in the sub-areas

• Protein-protein docking,
• Protein-ligand docking and
• Docking of DNA or RNA.

This division is necessary because the properties of the binding partner complex respectively involved in the call for the use of special algorithms.

• Computational Chemistry