Chemistry Reference
In-Depth Information
These include MACCS, rapid overlay of chemical structures (ROCS), extended-
connectivity fingerprints (ECFP) and phase SHAPE. It is also possible to use long
bit strings to encode 1D or 2D projections of molecular topology including as well
properties such pKa and logP. This can be complemented with additional
structural descriptor information, such as shape recognition data for identification
of active molecules.
The evaluation of docking methods is often based on their capacity to rank ligands
data sets consisting of known binders (with corresponding decoys/nonbinders). It
is necessary to pay attention to the physical properties of the compounds in the
decoy sets in order to obtain a fair assessment. Let us define physical similarity as
that among some physical properties such as (number of rotational bonds,
molecular weight, log P (cLogP), number of hydrogen bond acceptors and
donors). Let us also define chemical similarity to that involving chemical structure
such as (functional groups and molecular topology). These can be measured using
molecular fingerprints and Tanimoto similarity score. In most screening libraries
there are differences in chemical as well as physical properties. Unfortunately the
scoring functions used in docking sets can be undesirable influenced by physical
properties of the ligand. This would result in bias of the screening results.
The performance of similarity-based methods can also be affected by the
compounds structural classes. In these cases different approaches can generate
different results and show little overlap in similarity relationships.
MOLECULAR FIELDS
The molecular recognition between a ligand (the drug) and a macromolecule
(target) is a fundamental postulate in the classical drug design paradigm. H-
bonding, stacking, ionic and hydrophobic interactions are often observed in
ligand-protein interactions. Molecular electrostatic potentials are important.
Interaction forces can have inductive, dispersive and electrostatic components
[713-762].
Dispersion forces result from non-polar molecules (temporary dipoles in
neighboring molecules) and induce fluctuations in electron distribution in
