LigandScout
Encyclopedia
LigandScout is a software tool that allows to model 3D pharmacophore
models from structural data of macromolecule
/ligand
complexes or from training and test sets of organic molecules. It incorporates a complete definition of three-dimensional chemical features (such as hydrogen bond donors, acceptors, lipophilic areas, positively and negatively ionizable chemical groups) that describe the interaction of a bound small organic molecule
(ligand
) and the surrounding binding site
of the macromolecule
. These pharmacophores can be overlaid and superimposed using a pattern-matching based alignment algorithm that is solely based on pharmacophoric feature points instead of chemical structure. From such an overlay, shared features can be interpolated to create a so-called "shared-feature pharmacophore" that shares all common interactions of several binding sites/ligands or extended to create a so-called "merged-feature" pharmacophore. The software has been successfully used to predict new lead structures in drug design
, e.g. for the prediction of biological activity of novel HIV
reverse transcriptase inhibitor
s.
Pharmacophore
thumb|right|300px|An example of a pharmacophore model.A pharmacophore is an abstract description of molecular features which are necessary for molecular recognition of a ligand by a biological macromolecule....
models from structural data of macromolecule
Macromolecule
A macromolecule is a very large molecule commonly created by some form of polymerization. In biochemistry, the term is applied to the four conventional biopolymers , as well as non-polymeric molecules with large molecular mass such as macrocycles...
/ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
complexes or from training and test sets of organic molecules. It incorporates a complete definition of three-dimensional chemical features (such as hydrogen bond donors, acceptors, lipophilic areas, positively and negatively ionizable chemical groups) that describe the interaction of a bound small organic molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
(ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
) and the surrounding binding site
Binding site
In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...
of the macromolecule
Macromolecule
A macromolecule is a very large molecule commonly created by some form of polymerization. In biochemistry, the term is applied to the four conventional biopolymers , as well as non-polymeric molecules with large molecular mass such as macrocycles...
. These pharmacophores can be overlaid and superimposed using a pattern-matching based alignment algorithm that is solely based on pharmacophoric feature points instead of chemical structure. From such an overlay, shared features can be interpolated to create a so-called "shared-feature pharmacophore" that shares all common interactions of several binding sites/ligands or extended to create a so-called "merged-feature" pharmacophore. The software has been successfully used to predict new lead structures in drug design
Drug design
Drug design, also sometimes referred to as rational drug design or structure-based drug design, is the inventive process of finding new medications based on the knowledge of the biological target...
, e.g. for the prediction of biological activity of novel HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
reverse transcriptase inhibitor
Reverse transcriptase inhibitor
Reverse-transcriptase inhibitors are a class of antiretroviral drug used to treat HIV infection, tumors, and cancer. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase enzyme that retroviruses need to reproduce.-Mechanism:...
s.
See also
Other software tools which help to model pharmacophore include:- Software for molecular mechanics modeling
- Molecular Operating Environment (MOE) — by the Chemical Computing GroupChemical Computing GroupChemical Computing Group is a software company specializing in research software for computational chemistry, bioinformatics, cheminformatics, docking, pharmacophore searching and molecular simulation. The company's main customer base consists of pharmaceutical and biotechnology companies, as well...
- Phase — by Schrödinger
- Discovery Studio — by AccelrysAccelrysAccelrys is a software company headquartered in the US, with representation in Europe and Japan. It provides software for chemical, materials and bioscience research for the pharmaceutical, biotechnology, consumer packaged goods, aerospace, energy and chemical industries.Accelrys started in 2001...
- SYBYL-X — by Tripos
Further reading
- G. Wolber and R. Kosara. Pharmacophores from Macromolecular Complexes with LigandScout, chapter 6 in Pharmacophores and Pharmacophore Searches ISBN 3-527-31250-1 Table of contents and preface