title: 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.
abstract: 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, and uses the accurate and fast EPMM method. 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.
authors.affiliation: Chemistry Department, State University of New York at Buffalo, Buffalo, NY 14260-3000, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Anatoliy V
authors.initials: AV
authors.lastname: Volkov
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szalewicz
authors.forename: Philip
authors.initials: P
authors.lastname: Coppens
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002473:Cell Wall / Q000737:chemistry; D019295:Computational Biology / Q000379:methods*; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry; D011789:Quantum Theory; D055672:Static Electricity; D014640:Vancomycin / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D008024:Ligands; D010455:Peptides; C087127:balhimycin; D014640:Vancomycin