Current State-of-the-art for Virtual Screening and Docking Methods - New Developments in Medicinal Chemistry - page 99

DOCK in its original algorithm used a geometric matching algorithm to address
rigid body docking in order to superimpose the ligand onto a negative image of
the binding pocket. Force field scoring and on-the-fly optimization subsequently
introduced. Some releases incorporated improved matching algorithms for rigid
body docking as well as algorithm for flexible ligand docking. Subsequent
versions use the DMS program to generate a molecular surface for each receptor.
SPHGEN utility can be used to create the negative image of the surface.
SHOWBOX generates a receptor box centered on the ligand and GRID utility can
be used to pre calculate the scoring function potential grids [523].
MCDOCK carries out molecular docking operations automatically allowing for
the full flexibility of ligands in the docking calculations. The scoring function is
the sum of the interaction energy between the ligand and its receptor and the
conformational energy of the ligand. In this program, the Monte Carlo simulation
method is implemented to search for the global minimum whereas the final
scoring function is the detailed atomic interaction energy based upon molecular
mechanics [524].
RosettaLigand uses a sampling methodology to simultaneously optimize protein
backbone, protein side chain and ligand degrees of freedom. Energy functions and
algorithms used for stochastically exploiting protein and small molecule
conformations whereas the function consists of van der Waals, hydrogen bond,
implicit solvation terms as well as empirically derived torsional potentials. The
docking algorithm consists of gradient based minimization and stochastic Monte
Carlo moves. There is a pre-enumeration of major ligand conformations,
subjected to torsion space minimization during the simulation. For all receptor
side-chains. the rotamers in the binding site are optimized simultaneously using a
simulated annealing procedure. The receptor backbone is allowed to minimize
subject to restraints [525].
Q-DOCK LHM is a method for low-resolution refinement of binding poses
provided by FINDSITE LHM , a ligand homology modeling approach. In addition to
the pocket-specific contact potential derived from weakly related template
structures, the program uses position-specific anchor restraints imposed on the
predicted anchor binding modes. These are derived from weakly homologous