New version of the theoretical databank of transferable aspherical pseudoatoms, UBDB2011 – towards nucleic acid modelling

Abstract

The theoretical databank of aspherical pseudoatoms (UBDB) was recently extended with over 100 new atom types present in RNA, DNA and in some other molecules of great importance in biology and pharmacy. The atom-type definitions were modified and new atom keys added to provide a more precise description of the atomic charge-density distribution. X-H bond lengths were updated according to recent neutron diffraction studies and implemented in the LSDB program as well as used for modelling the appropriate atom types. The UBDB2011 databank was extensively tested. Electrostatic interaction energies calculated on the basis of the databank of aspherical atom models were compared with the corresponding results obtained directly from wavefunctions at the same level of theory (SPDFG/B3LYP/6-31G** and SPDFG/B3LYP/aug-cc-pVDZ). Various small complexes were analysed to cover most of the different interaction types, i.e. adenine-thymine and guanine-cytosine with hydrogen bonding, guanine-adenine with stacking contacts, and a group of neutral and charged species of nucleic acid bases interacting with amino acid side chains. The energy trends are well preserved (R(2) > 0.9); however the energy values differ between the two methods by about 4 kcal mol(-1) (1 kcal mol(-1) = 4.184 kJ mol(-1)) on average. What is noticeable is that the replacement of one basis set by another in a purely quantum chemical approach leads to the same electrostatic energy difference, i.e. of about 4 kcal mol(-1) in magnitude. The present work opens up the possibility of applying the UBDB2011 for macromolecules that contain DNA/RNA fragments. This study shows that on the basis of the UBDB2011 databank electrostatic interaction energies can be estimated and structure refinements carried out. However, some method limitations are apparent.

Quantum Crystallography: Current Developments and Future Perspectives

“…Nevertheless, the multipole modelc an provide ac harged ensity model as good as ad ouble-zeta basis-set representation, is mature and its application is fast. [102][103][104][105] Therefore, the multipole model allows to study many quantum phenomena, and to obtain ap redominantly experimental answer to research questionst hat depend on 1 r [99] With the ever-rising quality of experimental data, more and finer details of the electron density are observed with the help of the multipole model:c hemical bonds, lone pairs, crystal field effects on electron density of transition metals, [100] core region contraction upon chemical bond formation, [89] intermolecular charget ransfer [101] and electron density polarization upon interaction with neighboring molecules.…”

Electrostatic Interactions in Aminoglycoside-RNA Complexes

“…Computations included transforming the above prepared PDB files to shelx files and assigning UBDB atom types implemented in the LSDB program (29)(30)(31)54). Every nucleotide and aminoglycoside was scaled individually to its formal charge in LSDB.…”

“…The aspherical electron densities for various atom types are gathered in the University at Buffalo Databank (UBDB) (31) and can be applied to reconstruct the electron density of biomolecules. UBDB contains >200 atom types to cover atoms present in proteins, nucleic acids, and many organic molecules (29). Other similar data banks (32,33) have been developed and are compared in Bąk et al (34).…”

“…Among methods used to approximate electrostatics that go beyond the point-charge description, the approach based on the aspherical atom database (29)(30)(31) takes into account the asphericity of atomic electron density, contrary to point charges encountered in classical force fields. It assumes transferability of electron density, meaning that atoms in chemically equivalent vicinities have similarly deformed electron densities.…”

Molecular Electrostatic Potentials from Invariom Point Charges

“…The University of Buffalo Database (UBDB), [68] another scatteringfactor database that relies on the Hansen-Coppens multipole model, could in principle also be evaluated to provide point charges. To obtain scattering factors, the UBDB relies on quantum-chemical DFT single-point energy computations for selected crystal structures, which provide electron densities that are projected onto the multipole model and averaged.…”