Universal Method for Electrostatic Interaction Energies Estimation with Charge Penetration and Easily Attainable Point Charges

Abstract

Our new model of electron density augmented by point charges (aug-PROmol) provides an estimation of electrostatic interaction energies including penetration effects (ChemPhysChem 2016, 17, 2455–2460). In this paper we prove that it can be applied using sources of point charges other than those from direct restrained fitting to electrostatic potential (RESP). We used a newly established databank of tabulated invariom point charges and a widely known semiempirical method. Both sources perform equivalently to the basic aug-PROmol method as well as to reference energies at the DFT-SAPT/aug-cc-pVTZ level of theory. This is possible due to the universal character of the penetration model included in the aug-PROmol. Aug-PROmol may become a basis for development of new nonbonded terms in force fields or a high success rate scoring function.

New refinement strategies for pseudoatom databank - towards wider range of application

“…As an ultimate reference we used quantum mechanics values obtained at the DFT-SAPT/B3LYP/aug-cc-pVTZ level (Bojarowski et al, 2018). To validate if new models are better in the electrostatic energy estimation than already known models we used the results obtained from tailored UBDB approach (simultaneous refinement of all multipole model parameters) computed at the B3LYP/6-31G** as described in the 2.1.1 section, and from the aug-PROmol approach taken from our previous publications (Bojarowski et al, 2016;2018).…”

“…The Pv𝜅 model is significantly worse only for short distances in electrostatic dimers. Knowing the construction of the aug-PROmol model (Bojarowski et al, 2018), it can be concluded that expansion-contraction parameters are very important and their fine tuning may lead in the future to even better results.…”

“…The RESP point charges are derived externally, on demand for a molecule in question, following procedures widely used in the molecular mechanics field. Alternatively, RESP charges can be taken from the Invariom Point Charges database (Bojarowski et al, 2018). The aug-PROmol model is spherical by design what allows to speed up energy calculation by omitting time consuming integration.…”

Combining Molecular Dynamic Information and an Aspherical-Atom Data Bank in the Evaluation of the Electrostatic Interaction Energy in Multimeric Protein-Ligand Complex: A Case Study for HIV-1 Protease

“…It is unable to take into account such phenomena as electron polarization, subtle details of electron density anisotropy, and charge penetration. Considerable efforts have been devoted to provide a more realistic description of intermolecular interactions by including the aforementioned aspects with recent emphasis on penetration energy (Epen) [15][16][17][18][19][20][21][22][23][24][25]. Here we based our analysis on the University at Buffalo Databank (UBDB) of transferable atomic densities [26][27][28], from which the charge densities of protease-inhibitor complexes was reconstructed.…”

Combining Molecular Dynamic Information and an Aspherical-Atom Data Bank in the Evaluation of the Electrostatic Interaction Energy in Multimeric Protein-Ligand Complex: A Case Study for HIV-1 Protease

“…Considerable efforts have been devoted to provide a more realistic description of intermolecular interactions by including the aforementioned aspects with recent emphasis on penetration energy (Epen). [12][13][14][15][16][17][18][19][20][21][22] The analysis is based on a data bank of transferable atomic densities [23][24][25] , from which the charge density of the protease-inhibitor complexes is reconstructed. Electrostatic interaction energies are then evaluated using an exact algorithm for the short-range interactions and the Buckingham approximation for non-overlapping densities for atoms at large distances 26 .…”