Docking thesis

Theory of docking. Essentially, the aim of molecular docking is to give a prediction of the ligand-receptor complex structure using computation methods. Docking can be achieved through two interrelated steps: first by sampling conformations of the ligand in the active site of the protein; then ranking these conformations via a scoring function.

The docking process involves two basic steps: prediction of the ligand conformation as well as its position and orientation within these sites (usually referred to as pose) and assessment of the binding affinity. These two steps are related to sampling methods and scoring schemes, respectively, which will be discussed in the theory section.

Typically the process starts with a target of known structure, such as a crystallographic structure of an enzyme of medicinal interest. Docking is then used to predict the bound conformation and binding free energy of small molecules to the target.

Exhaustive enumeration of ligand torsions generates a collection of ligand conformations that are examined during the docking process. Given these ligand conformations, initial screens are deterministically performed over the entire phase space available to the ligand to locate promising ligand poses.