LigandScout
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 3D 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.[1] These pharmacophores can be overlaid and superimposed using a pattern-matching based alignment algorithm[2] 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 inhibitors.[3]
See also
Other software tools which help to model pharmacophore include:
- Software for molecular mechanics modeling
- Molecular Operating Environment (MOE) — by the Chemical Computing Group
- Phase — by Schrödinger
- Discovery Studio — by Accelrys
- SYBYL-X — by Tripos
References
- ↑ Wolber G, Langer T (2005). "LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters". J Chem Inf Model 45 (1): 160–169. doi:10.1021/ci049885e. PMID 15667141.
- ↑ Wolber G, Dornhofer AA, Langer T (2007). "Efficient overlay of small organic molecules using 3D pharmacophores". J Comput Aided Mol Des 20 (12): 773–788. doi:10.1007/s10822-006-9078-7. PMID 17051340.
- ↑ Barreca ML, De Luca L, Iraci N, Rao A, Ferro S, Maga G, Chimirri A (2007). "Structure-based pharmacophore identification of new chemical scaffolds as non-nucleoside reverse transcriptase inhibitors". J Chem Inf Model 47 (2): 557–562. doi:10.1021/ci600320q. PMID 17274611.
Further reading
- Wolber G, Kosara R. "Chapter 6: Pharmacophores from Macromolecular Complexes with LigandScout". Pharmacophores and Pharmacophore Searches. Wiley. ISBN 3-527-31250-1.