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Interaction energies between glycopeptide antibiotics and substrates in complexes determined by X-ray crystallography: application of a theoretical databank of aspherical atoms and a symmetry-adapted perturbation theory-based set of interatomic potentials

✍ Scribed by Li, Xue ;Volkov, Anatoliy V. ;Szalewicz, Krzysztof ;Coppens, Philip


Publisher
International Union of Crystallography
Year
2006
Tongue
English
Weight
833 KB
Volume
62
Category
Article
ISSN
0907-4449

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✦ Synopsis


Intermolecular interaction energies between fragments of glycopeptide antibiotics and small peptide ligands are evaluated using geometries determined by X-ray crystallography and recently developed methods suitable for application to very large molecular complexes. The calculation of the electrostatic contributions is based on charge densities constructed with a databank of transferable aspherical atoms described by nucleus-centered spherical harmonic density functions [Volkov et al. (2004), J. Phys. Chem. 108, 4283-4300], and uses the accurate and fast EPMM method [Volkov et al. (2004), Chem. Phys. Lett. 391,[170][171][172][173][174][175]. Dispersion, induction and exchange-repulsion contributions are evaluated with atom-atom potentials fitted to intermolecular energies from SAPT (symmetry-adapted perturbation theory) calculations on a large number of molecules. For a number of the complexes, first-principle calculations using density functional theory have been performed for comparison. Results of the new methods agree within reasonable bounds with those from DFT calculations, while being obtained at a fraction (less than 1%) of the computer time. A strong dependence on the geometry of the interaction is found, even when the number of hydrogen bonds between the substrate and antibiotic fragment is the same. While high-resolution X-ray data are required to obtain interaction energies at a quantitative level, the techniques developed have potential for joint X-ray/ energy refinement of macromolecular structures.