Chemistry Reference
In-Depth Information
to receptors (fully automatically and done by computational chemists for use by
medicinal chemists). It yields large enrichment factors and a high percentage of
active compounds recovered [535].
3d-QSAR+CoMFA+CoMSIA+FlexX-Dock
is a protocol for predicting
competitive inhibitors. 3D-QSAR was built and validated based upon known
inhibitors by means of comparative molecular field analysis (CoMFA) and
comparative molecular similarity indices analysis (CoMSIA). The FlexX-dock
program is employed to screen the database against the desired target. The 3d-
QSAR models predicts from the virtual hits, the inhibitors with activity within the
desired range. The protocol combines ligand-and structure-based approaches
being capable of identifying new hits with topologically diverse scaffolds [536].
H-DOCK
is a fast protein-ligand docking algorithm based on hydrogen bond
matching and surface shape complementarity. First a divide-and-conquer strategy
enumeration-based approach is used to rank the intermolecular modes between
ligand and protein maximizing their hydrogen bonds matching. Each docked
conformation of the ligand is calculated according to the matched hydrogen
bonding geometry. A simple but effective scoring function, reflecting mostly van
der Waals interactions, is used to evaluate the docked conformations of the ligand.
For flexible docking, the rigid docking procedure is repeated for multiple
conformations of a small molecule (ranking all together). Authors suggest that
hydrogen bonding and steric hindrance can grasp the key interactions between
ligand and protein [537].
GalaxyDock
is a protein-ligand docking program with flexible protein-side
chains. It accounts for the flexibility of preselected receptor side-chains by global
optimization of energy based functions trained for flexible side-chain docking.
The energy function is a linear sum of protein-ligand, intraligand interaction
energy and intraprotein energy. The receptor is treated as rigid and the
conformational sampling is based on conformational space annealing (global
optimization). A fixed number of docking conformations referred to as a bank is
generated and evolved until convergence [538].
