Extension of the transferable aspherical pseudoatom data bank for the comparison of molecular electrostatic potentials in structure–activity studies

Abstract

The transferable aspherical pseudoatom data bank, UBDB2018, is extended with over 130 new atom types present in small and biological molecules of great importance in biology and chemistry. UBDB2018 can be applied either as a source of aspherical atomic scattering factors in a standard X-ray experiment (d min ' 0.8 Å ) instead of the independent atom model (IAM), and can therefore enhance the final crystal structure geometry and refinement parameters; or as a tool to reconstruct the molecular charge-density distribution and derive the electrostatic properties of chemical systems for which 3D structural data are available. The extended data bank has been extensively tested, with the focus being on the accuracy of the molecular electrostatic potential computed for important drug-like molecules, namely the HIV-1 protease inhibitors. The UBDB allows the reconstruction of the reference B3LYP/6-31G** potentials, with a root-mean-squared error of 0.015 e bohr À1 computed for entire potential grids which span values from ca 200 e bohr À1 to ca À0.1 e bohr À1 and encompass both the inside and outside regions of a molecule. UBDB2018 is shown to be applicable to enhancing the physical meaning of the molecular electrostatic potential descriptors used to construct predictive quantitative structure-activity relationship/quantitative structure-property relationship (QSAR/QSPR) models for drug discovery studies. In addition, it is suggested that electron structure factors computed from UBDB2018 may significantly improve the interpretation of electrostatic potential maps measured experimentally by means of electron diffraction or single-particle cryo-EM methods.

Refinement of Organic Crystal Structure with Multipolar Electron Scattering Factors

“…Generally, the IAM potential is too positive in both, the electron pair regions and in the covalent bonding regions, and not positive enough in the regions surrounding the polar hydrogen atoms. All the observations are similar to these we already noted among many other organic molecules (Kumar et al, 2019).…”

“…It incorporates the IAM and TAAM models of X-ray or electron scattering factors available in DiSCaMB library (Chodkiewicz et al, 2018) (Cowley et al, 2006) was used. To parametrize TAAM, the newest version (Kumar et al, 2019) of the UBDB databank (Volkov, Li et al, 2004;Dominiak et al, 2007;Jarzembska & Dominiak, 2012) was used together with LSDB (Volkov, Li et al, 2004). The parameters were transferred after first cycles of the IAM refinements done during structure solution step.…”

“…Therefore it was possible to build a databank of different types of pseudoatoms and to use the databank to generate a transferable aspherical atom model (TAAM) parameters for any organic molecule, up to and including proteins and nucleic acids. There are three major pseudoatom databanks available at the moment: ELMAM2 (Zarychta et al, 2007;Domagała & Jelsch, 2008;Domagała et al, 2011Domagała et al, , 2012, the Invariom database called GID (Dittrich et al, 2006(Dittrich et al, , 2013 and the University at Buffalo Pseudoatom Databank (UBDB) (Koritsanszky et al, 2002;Volkov, Li et al, 2004;Dominiak et al, 2007;Jarzembska & Dominiak, 2012;Kumar et al, 2019). They differ principally in the sources used to define the pseudoatom parameters and in the method by which atom types are defined.…”

Mapping molecular electrostatic potential for heme interacting with nano metal oxides

“…The electrostatic potential V(r) of a molecule always confirms a significant role in guiding its reactive behavior. For biological as well as organic molecules, MESP gives significant descriptions for such molecules and considered excellent descriptors for their possible interactions [23][24][25][26][27][28][29][30][31].…”

Refinement of Organic Crystal Structure with Multipolar Electron Scattering Factors

“…Since 2005 we have been involved in the development of the UBDB (Kumar et al, 2019;Jarzembska & Dominiak, 2012;Dominiak et al, 2007). Currently the UBDB contains atom-types occurring in proteins, nucleic acids and many organic molecules.…”