Current State-of-the-art for Virtual Screening and Docking Methods - New Developments in Medicinal Chemistry - page 92

used has two major stages. A cavity detection algorithm used in the first step to
identify potential binding sites. The second step consists of fitting the given ligand
to a specified binding site. A Monte Carlo conformational sampling procedure is
used which is guided by a shape-based filter necessary to generate binding poses
matching the binding site. The DockScore energy function is used to perform
rigid body energy minimization on candidate binding poses. Further ligand
binding poses can be evaluated using external scoring functions [494].
eHITS is an unusual fragment-based docking program which is based on
individually docked fragments. The program tries to find a global optimum. First
a grid is created inside the active site of the protein with equal spacing of 0.5 Å
whereas the ligand is divided into rigid fragments connected by linkers that are
flexible. Each fragment is docked independently to the active site at every
possible place via geometrical criteria with a scoring for each case without
discarding any fragments. Secondly, the hyper-graph detection algorithm matches
rigid fragments that are compatible. The best-suited combination of fragments is
chosen for further studies. Subsequently, there is an attempt by the algorithm to
connect ligand fragments with flexible linkers in order to recreate the ligand
structure. Then, in the given active site of the receptor, the energy minimization is
performed with the possibility of rigid translation and torsion angles. Knowledge-
based scoring functions are used to predict the ligand binding affinity [495].
FlexX is a traditional fragment-based docking tool whereas the choice of the
fragment (ligand based) is the key step since it makes the ligand core responsible
for principal interactions with the protein target. The database of torsion angles is
used to generate different poses of a fragment that is considered as rigid in further
steps. The selected fragment is placed in the active site of the protein and
alignment procedure is attempted to establish favorable interactions. For docking
of each fragment, steric distortions are removed and the interaction energy
estimated. The procedure is repeated for other fragments of the ligand. The ligand
is reconstructed in an incremental manner [496].
F RED input consists of conformers for each ligand for a two stage docking
procedure (shape fitting and optimization). During the first stage, a 0.5 Å-
resolution grid is used for placing the ligand. All atoms of the active site are