Chemistry Reference
In-Depth Information
clashes; methods based on the selection of a small set of essential degrees of
freedom in the binding site; ensemble-based methods; molecular simulation
methods modified for flexible receptor docking and methods based on collective
degrees of freedom.
Full induced-fit docking approaches for moderate plasticity are becoming
available yielding non-prohibitive docking applications including side-chain
modeling and automated approaches. However if complicated energetic effects
are involved, small conformational changes of few side chains may yield
unexpected results. More progress is also required for scoring (localized backbone
motions as well as flexible-protein docking benchmarking) [270-320].
CHEMOGENOMIC APPROACHES
Only a very small fraction of compounds describing the current chemical space
has been tested on an also very small fraction of the entire target space.
Chemogenomics is an interdisciplinary field. It attempts to match target and
ligand space and ultimately identify ligands of targets. Receptors are grouped into
sets of related receptor families that can be explored in a systematic manner and
derive predictive links between the chemical structures of receptors and
interacting bioactive molecules.
Regarding chemogenomics, we note that there are various definitions of
overlapping fields (chemical genetics, chemical genomics). A broad definition of
chemogenomics encompasses chemoproteomics (the study of small-molecular-
weight drug candidates on gene/protein function). Chemogenomics is at the
interface of chemistry, biology and informatics (data mining). Borderline
methodologies (medicinal chemistry, chemoinformatics, bioinformatics) play
major roles in bringing these major disciplines together.
For drug discovery, chemogenomic approaches to drug discovery require
target/compound libraries, high-throughput binding and functional assays or
gene/protein expressions.
Predictive chemogenomics can attempt to predict compounds-genes/proteins
relationships, target selectivity for various ligands as well as ligand selectivity for
