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

• Published in: Acta crystallographica. Section A, Foundations and advances Foundations and advances, 2019-03, Vol.75 (2), p.398-408
• Main Authors: Kumar, Prashant, Gruza, Barbara, Bojarowski, Sławomir Antoni, Dominiak, Paulina Maria
• Format: Article
• Language: English
• Subjects: aspherical scattering factors; Charge density; Charge distribution; Computation; Crystal structure; Data banks; Density distribution; electron crystallography; Electron diffraction; Electronic structure; electrostatic potential; Electrostatic properties; HIV; Human immunodeficiency virus; Molecular structure; Organic chemistry; Protease inhibitors; Proteinase inhibitors; pseudoatom data bank; quantum crystallography; structure refinement; Structure-activity relationships; transferable aspherical atom model (TAAM); UBDB2018; X‐ray diffraction
• ISSN: 2053-2733; 0108-7673; 2053-2733
• DOI: 10.1107/S2053273319000482

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 (dmin ≃ 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−1 computed for entire potential grids which span values from ca 200 e bohr−1 to ca −0.1 e bohr−1 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. The transferable aspherical pseudoatom data bank, UBDB2018, is extended with over 130 new atom types present in small and biological molecules of importance in biology and chemistry. UBDB2018 can be used to enhance the physical meaning of molecular electrostatic potentials which can be utilized in, amongst other fields, drug discovery studies.