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Docking Into Artifical Receptors Using Gold: Background
Supramolecular chemistry is a large and important area of research.
There is much interest in host-guest systems, where researches aim to design
receptors for molecules to achieve selective binding and/or the catalysis of reactions.
Much of this research is inspired by biological systems where the receptors (hosts) are proteins.
With this relation it is only natural that computational tools employed to study protein-ligand interactions
are extended to the study of supramolecular host-guest systems.
Although GOLD has been designed to dock small drug-like molecules to
proteins it can also be used to dock guest molecules to
artificial receptors. GOLD relies on atom-type interactions and since many interactions
in artificial organic host-guest systems are similar to protein-ligand systems,
GOLD is a viable tool to explore these binding conformations. Here we present two case-studies with the
macrocyclic receptor cucurbit[n]uril.
Figure 1 Cucurbit[7]uril
Cucurbit[6]uril was first discovered in 1905, the macrocycle is formed by a
condensation reaction of glycoluril and formaldehyde in concentrated HCl. The structure and
subsequent applications of cucurbit[n]uril were not fully realised until the beginning of the 1980s,
for more information about cucurbit[n]uril, please refer to the comprehensive review in Angew. Chem. Int. Ed. 2005, 44, 4844.
Today the cucurbit[n]uril family has been extended to include cycles with n = 5, 7, 8, and 10 and several derivates of
these. Cucurbit[n]uril has derived its name from its pumpkin shape, the structure is
relative rigid and contains a cavity accessible by two carbonyl-lined portals (see Figure 1).
The carbonyl oxygens lining the two portals make for excellent binding of cations while the core
is hydrophobic (see Figure 2).
Figure 2 Electrostatic potential map of Cucurbit[7]uril
Artificial Receptors: Example 1
Artificial Receptors: Example 2
For two further recent examples of docking to artificial receptors, please see:
- A. Amadasi, C. Dall'Asta, G. Ingletto, R. Pela, R. Marchelli, P. Cozzini, Explaining cyclodextrin-mycotoxin interactions using a "natural" force field, Bioorganic & Medicinal Chemistry (2007), 10.1016/j.bmc.2007.04.006
- A. Steffen, C. Thiele, S. Tietze, C. Strassing, A. Kamper, T. Lengauer, G. Wenz, J. Apostolakis, Improved Cyclodextrin-Based Receptors for Camptothecin by Inverse Virtual Screeining, Chemistry, A European Journal (2007), 10.1002/chem.200700661
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