Development of the ABEEMσπ Polarization Force Field for Base Pairs with Amino Acid Residue Complexes

Abstract

DNA damage caused by oxidized bases can lead to aging and cancer in living beings. Luckily, a repair enzyme is able to repair the oxidized bases. The key step is to accurately recognize the oxidized bases, which mainly rely on complex hydrogen bond interactions. We have calibrated the charge parameters and torsional parameters of the ABEEMσπ polarization force field (ABEEMσπ PFF) to accurately describe the intermolecular and intramolecular interactions. Taking the experiment and quantum chemical method as the benchmark, a series of properties of base pair-amino acid residue systems, DNA and DNA-protein interaction systems were calculated and compared with those of other force fields. We have done a tremendous amount of tasks in testing, calibrations, and analyses. The ABEEMσπ PFF not only explicitly gives the position and the partial charge of lone-pair electrons but also introduces a function k to fit special electrostatic interactions in hydrogen bond interaction regions. Therefore, it can accurately simulate the polarization effect and charge transfer of hydrogen bond interactions, especially for charged systems and sulfur-containing systems, such as the binding energy between amino acid and base pairs (24-28 kcal/mol), which is induced by charge transfer. The RMSD of ABEEMσπ PFF is 1.18 kcal/mol, whereas the RMSD of Amber OL15 is 8.21 kcal/mol. The relative positions of the amino acid residue have significantly changed, and the hydrogen bonds were broken when simulated by fixed charge force fields. In addition, owing to refitting the reasonable torsional parameters, the geometric structures optimized by ABEEMσπ PFF were well consistent with those of the M06-2X/6-311++G** method, but the simulations by fixed force fields have a large rotation of methyl and distortion of the plane of the base pair. After extensive MD simulation with four test DNAs and a DNA-protein system, we conclude that ABEEMσπ PFF shows better agreement when compared to experimental structures, which illustrates the reliability of our model and the transferability of the parameters.

Reaction mechanism of NO with hydrolysates of NAMI‐A: an MD simulation by combining the QM/MM(ABEEM) with the MD‐FEP method

“…Wilson and Ichikawa and Torrent‐Sucarrat and coworkers pointed out that the charge transfer between atoms in a molecule is overestimated by using the polarization basis sets. Huzinaka et al, Jakalian et al, Watanabe et al, and our group have shown that the use of higher levels of basis sets overestimates the overlap between their respective basis functions belonging to two atoms in a molecule. Bayly and his coworkers pointed out that when the 6‐31G* basis set is used, the polarity of a molecule calculated by the partial charges is overestimated by 10%–15% .…”

Fukui Function and Local Softness Related to the Regioselectivity of Electrophilic Addition Reactions

“…Based on the DFT and electronegativity equalization method (EEM) [28][29][30][31][32][33][34] , Yang and his coworkers have developed ABEEM model [35][36][37][38][39][40][41][42][43][44][45] , which explicitly partitions a molecule into atom, chemical bond, and lone pair (lp) regions. In this model, the single bond consists of one  region, where the center of the charge for  bond is located on the position of the ratio of the covalent atomic radii of two bonded atom; the double bond consists of one  region and four π regions, where center of the  bond charge is similar with the σ region of single bond and the  bond partial charges are placed above and below the double-bonded atoms at the covalent radii of the this double-bonded atoms perpendicular to the plane formed by the  bond; and the center of charge and its orientation for the lp region is determined in terms of the chemical surrounding.…”

“…a and b denote two regions, including the atom or single bond  or double bond  and  or lone pairs regions. qa and qb are the partial charges of regions a and b, Ra,b denotes the distance between regions a and b, and k, 0.57, is an overall correction coefficient in this formalism 22,[35][36][37][38][39][40][41][42][43][44][45][46][47] . The electronegativity equalization principle demands that the effective electronegativity of every region is equal to the overall electronegativity of the molecule, χmol:…”

“…Then the charge distributions obtained for the model molecules were brought into Eqs. (7)(8)(9) in order to determine the parameters χ * and 2η * through a regression and least-squares optimization procedure 22,[35][36][37][38]46,47 . The old types of parameters were obtained from our previous work 37 , and the new added types and parameters of χ * and 2η * are listed in Table 1.…”

A model of atoms in molecules based on potential acting on one electron in a molecule: I. Partition and atomic charges obtained from ab initio calculations

“…Atomic charges of this type are based on the concept of electronegativity. Some methods based on the electronegativity equalization principle in DFT have been developed, such as Mortier's electronegativity equalization method (EEM); the split charge equilibration (SQE) model; Rappé and Goddard's QEq; York and Yang's chemical potential equilibration (CPE); the partial equalization of orbital electronegativity proposed by Gasteiger et al and Scheraga and coworker; the methods proposed by Mullay and Abraham and coworkers; and Yang's atom‐bond electronegativity equalization method (ABEEM), among others …”