Current State-of-the-art for Virtual Screening and Docking Methods - New Developments in Medicinal Chemistry - page 93

considered, including hydrogen, via a smooth Gaussian potential. Three
optimization filters are processed, i.e. refining of hydroxyl hydrogen position,
rigid body optimization and optimization in the dihedral angle space of the ligand
pose. For optimization, scoring functions are used (ChemScore, Gaussian shape
scoring, ScreenScore) [497].
HYBRID uses both the structure of the target protein and the ligand bound to the
active site to pose and score ligands. The program is also capable of using
multiple conformation of the target protein if more than one crystallographic
structure is available. The docking and scoring algorithms are similar to that of
FRED [498].
SURFLEX , can be divided into two stages. An ideal ligand fitting to the binding
site is done at the first stage generating protomol. Different types of molecular
fragments (hydrogen bond donor group, hydrophobic group, bond acceptor group)
are placed into the binding site of the protein with the orientations and positions
optimized to form maximum interactions with the protein. Protomol is formed by
assembling top-scored fragments. An incremental algorithm is used in the second
step to find optimal binding poses of the given ligand. This is first broken into
fragments with their conformations explored. There is subsequent alignment to
the corresponding regions on the protomol evaluated by their steric
complementarity to the binding site as well as binding scores. This yields a
complete molecule generated by incremental construction from top-scored
fragments or from a crossover operation combining intact molecules. Final
binding poses submitted to in situ comformational optimization using binding
scores computed by the Jain scoring functions [499].
TMFS is a novel rapid computational proteochemometric method called train,
match, fit, streamline (TMFS) which proposes to map new drug-target interaction
space and predict new uses. The TMFS method combines shape, topology and
chemical signatures, including docking score and functional contact points of the
ligand, to predict drug-target interactions [500].
DARC is a structure-based computational docking approach using Ray Casting
for carrying out virtual screening by docking small-molecules into protein surface