Kirchhoff atomic charges fitted to multipole moments: Implementation for a virtual screening system

Abstract

The Kirchhoff charge model is a viable method of generating inexpensive and electrostatically reasonable atomic charges for molecular mechanical force fields. The charging method uses a computationally fast algorithm based on the principle of electronegativity relaxation. Parameters of the method, orbital electronegativities and hardnesses, are fitted to reproduce reference, ab initio calculated dipole and quadrupole moments of a representative training set of neutral and charged organic molecules covering most medicinal chemistry relevant bonding situations. Transferability and accuracy of the derived parameters are confirmed on an external test set. Comparisons to other charge models are made. Implementation of the new Kirchhoff charges into a virtual screening engine is elucidated.

General Purpose Electronegativity Relaxation Charge Models Applied to CoMFA and CoMSIA Study of GSK‐3 Inhibitors

“…KCM and DENR charges were calculated with in-house programs. Parameters for KCM are published and can be found elsewhere, [34] while the DENR parameters are given in the Supporting Information. The calculation of GH, MMFF94 and PLM charges was done with Sybyl.…”

“…[33] The KCM model was parameterized to reproduce ab initio calculated dipole and quadrupole moments and finally implemented in a virtual screening routine. [34] The most recent extension of the Kirchhoff Charge Model is the Dynamic Electronegativity Relaxation [35] (DENR), which provides a unified description framework for several known charge schemes based on incomplete electronegativity equalization. DENR parameters were fitted to reproduce ab initio (HF/6-31G*) calculated MEP.…”

Design, synthesis and evaluation of 3-quinoline carboxylic acids as new inhibitors of protein kinase CK2

“…24 , except for grid spacing that was set to 0.3. Calculations of ligand geometry were performed using YFF force field developed by the authors 25 , partial atomic charges of the ligands were calculated with Kirchhoff method 26,27 . For receptor-ligand flexible docking the DOCK program has been used.…”

Design, synthesis and evaluation of 2-phenylisothiazolidin-3-one-1,1-dioxides as a new class of human protein kinase CK2 inhibitors

“…Calculations of ligand geometry were performed using YFF force field developed by the authors 6,7 . Partial atomic charges of the ligands were calculated with the Kirchhoff method 8 . Minimization of CK2 crystal structure (PDB ID: 2ZJW) was performed with GROMACS 9 package (Biophysical Chemistry Department of University of Groningen, AB Groningen, The Netherlands) (steepest descent algorithm, GROMACS force field).…”