Name
Abstract | ||
|---|---|---|
In this study we investigate pi-stacking interactions of a variety of aromatic heterocycles with benzene using dispersion corrected density functional theory. We calculate extensive potential energy surfaces for parallel-displaced interaction geometries. We find that dispersion contributes significantly to the interaction energy and is complemented by a varying degree of electrostatic interactions. We identify geometric preferences and minimum interaction energies for a set of 13 5- and 6-membered aromatic heterocycles frequently encountered in small drug-like molecules. We demonstrate that the electrostatic properties of these systems are a key determinant for their orientational preferences. The results of this study can be applied in lead optimization for the improvement of stacking interactions, as it provides detailed energy landscapes for a wide range of coplanar heteroaromatic geometries. These energy landscapes can serve as a guide for ring replacement in structure-based drug design. |
Year | DOI | Venue |
|---|---|---|
2014 | 10.1021/ci500183u | JOURNAL OF CHEMICAL INFORMATION AND MODELING |
Keywords | Field | DocType |
drug design,static electricity,thermodynamics,quantum theory | Electrostatics,Dispersion (optics),Chemical physics,Molecule,Combinatorial chemistry,Computational chemistry,Chemistry,Potential energy,Interaction energy,Density functional theory,Static electricity,Stacking | Journal |
Volume | Issue | ISSN |
54 | 5 | 1549-9596 |
Citations | PageRank | References |
3 | 0.52 | 2 |
Authors | ||
7 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Roland G. Huber | 1 | 11 | 2.89 |
| Michael A. Margreiter | 2 | 3 | 0.52 |
| Julian E Fuchs | 3 | 25 | 5.51 |
| Susanne von Grafenstein | 4 | 11 | 1.54 |
| Christofer S. Tautermann | 5 | 67 | 5.42 |
| Klaus R Liedl | 6 | 102 | 17.06 |
| Thomas Fox | 7 | 18 | 2.70 |