Chemistry Reference
In-Depth Information
and third-order (new parametrizations scheme) models with applications to
organic and biological systems [655, 656]. The modifications allegedly leads to
improved overall performance [657].
QM/MM (quantum mechanics/molecular mechanics is an approach that can be
used to approximate binding affinities. The basic premise is the combination of
the strength of both QM (more accurate) and MM (efficient, faster) methods to
generate a strong tool for investigation of systems (including biological) which
are divided into two regions. The inner region is treated quantum-mechanically
whereas the outer region can be described by a force field addressed respectively
as QM and MM regions [366,374-380].
The ligand would be the QM region for a protein-ligand complex whereas the
protein would be the MM region. Special attention needs to be paid to the
boundary between inner and outer regions. QM/MM methods were originally
used for modeling reactions in biological systems and gradually emerged as
important tools for predicting biological activity of inhibitors. They indicate good
correlation between computed interaction energies and biological activities of
inhibitors. The model provides good potential to improve the interaction energy of
the lead compounds with a reasonable computational cost [374-380].
SIMILARITY-BASED
Since structurally similar compounds can have similar biological and
physiochemical properties, similarity-based VS have become an important part of
in silico
drug discovery. This protocol permits fast identification of biologically
active analogues. However, adequate representation of the molecules involved is
required. These representations include one-dimensional descriptors (log P), 2D
descriptors (MACCS structural keys), 3D descriptors, spatial pharmacophores
(CoMFA fields) [200, 239, 381-392, 458, 534, 537, 713-799].
The fingerprints calculated from a molecule's geometry, as with human
fingerprints, may be sufficiently detailed whereas comparing two molecular
fingerprints may be almost equivalent to comparing the molecules themselves
[381-383]. VS often use the 2D fingerprint and 3D shape similarity methods.
