Various atomic charge calculation schemes of CoMFA on HIF‐1 inhibitors of moracin analogs

Selection of appropriate partial charges in a molecule is crucial to derive good quantitative structure–activity relationship models. In this work, several partial atomic charges were assigned and tested in a comparative molecular field analysis (CoMFA) models. Many CoMFA models were generated for a series of hypoxia inducible factor 1 (HIF‐1) inhibitors using various partial atomic charges including charge equalization, Mülliken population analysis (MPA), natural population analysis, and electrostatic potential (ESP)‐derived charges. These atomic charges were investigated at various theoretical levels such as empirical, semiempirical, Hartree–Fock (HF), and density functional theory (DFT). Among them, Merz‐Singh‐Kollman (MK) ESP‐derived charges at the level of HF/6‐31G* gave the highest predictive q² with experimental pIC₅₀ values. With this charge scheme, a detailed analysis of CoMFA model was performed to understand the electrostatic interactions between ligand and receptor. More elaborate charge calculation schemes such as HF and DFT correlated more strongly with activity than empirical or semiempirical schemes. The choice of optimization methods was important. As geometries were fully optimized at the given levels of theory, the aligned structures were different. They differed considerably, especially for the flexible parts. This was likely the source of the substantial variation of q² values, even when the same steric factor was considered without electrostatic parameters. ESP‐derived charges were most appropriate to describe CoMFA electrostatic interactions among MPA, NBA, and ESP charges. Overall q² values vary considerably (0.8–0.5) depending on the charge schemes applied. The results demonstrate the need to consider more appropriate atomic charges rather than default CoMFA charges. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

Analysis of the Interaction Between Bacillus coagulans and Bacillus thuringiensis S-layers and Calcium Ions by XRD,Light Microscopy,and FTIR

S-layer is a self-assemble regularly crystalline surface that covers major cell wall component of many bacteria and archaea and exhibits a high metal-binding capacity. We have studied the effect of the calcium ions and type of solid support (glass or mica) on the structure of the S-layers from Bacillus coagulans HN-68 and Bacillus thuringiensis MH14 upon simple methods based on light microscopy and AFM. Furthermore, the Fourier transform infrared spectroscopy (FTIR) study is indicated that the calcium–S-layer interaction occurred mainly through the carboxylate groups of the side chains of aspartic acid (Asp) and glutamic acid (Glu) and nitrogen atoms of Lys, Asn, and histidine (His) amino acids and N–H groups of the peptide backbone. Studied FTIR revealed that inner faces of S-layer are mainly negative, and outer faces of S-layer are mainly positive. Probably, calcium ions with positive charges bound to the carboxyl groups of Glu and Asp. Accordingly, calcium ions are anchored in the space between the inner faces of S-layer with negative charge and the surface of mica with negative charge. This leads to regular arrangement of the S-layer subunits.     

Effects of pH,salt, surfactant and composition on phase transition of poly(NIPAm/MAA) nanoparticles

The volume phase transition of poly(NIPAm/MAA) copolymer nanoparticles in buffer solutions at various pH and in aqueous solutions of KCl or ionic surfactants (SDS and DTMAB) was systematically studied using dynamic laser scattering technique. It was found that ionizable MAA groups imparted a responsiveness of the particles to pH and electrolytes. At pH > pKa of the copolymer, electrostatic repulsion of negative charges, mostly from COO⁻ groups, was a governing mechanism for preventing the particles from collapse at T > T_tr. The particles exhibited a sharp volume phase transition upon elimination of the negative charges by decreasing the pH of the medium or by the addition of cationic surfactant. At pH < pKa, the presence of MAA groups enhanced the hydrophobicity of the particles as indicated by a lower T_tr and a sharper volume phase transition. A pH 4 buffer at the same ionic strength exhibited the most significant effect on the particle size and phase transition, followed by the ionic surfactant with an opposite charge (e.g., DTMAB), KCl, and finally the ionic surfactant with the same charge (e.g. SDS). © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2667–2676, 1999     

Double Layer at the Pt(111)–Aqueous Electrolyte Interface: Potential of Zero Charge and Anomalous Gouy–Chapman Screening

We report, for the first time, the observation of a Gouy–Chapman capacitance minimum at the potential of zero charge of the Pt(111)‐aqueous perchlorate electrolyte interface. The potential of zero charge of 0.3 V vs. NHE agrees very well with earlier values obtained by different methods. The observation of the potential of zero charge of this interface requires a specific pH (pH 4) and anomalously low electrolyte concentrations (<10^?3 m ). By comparison to gold and mercury double‐layer data, we conclude that the diffuse double layer structure at the Pt(111)‐electrolyte interface deviates significantly from the Gouy–Chapman theory in the sense that the electrostatic screening is much better than predicted by purely electrostatic mean‐field Poisson–Boltzmann theory.     

The impact of the modified Poisson–Boltzmann model on protein bound to a lipid coated silicon nanowire field effect transistor biosensor in an electrolyte environment

The aim of this work was to analyse the electrostatic potential profile, various effects of electrolyte concentrations, and the influences of surface charge on a protein bound to a lipid coated Silicon nanowire field effect transistor (Si-NW FET) biosensor by implementing the modified Poisson–Boltzmann (MPB) model. In this work, we modelled a lipid monolayer-coated Si-NW FET for the sensing of proteins, which consisted of variable amounts of aspartic acid. The electrostatic potential profile, protein charge distributions, the response to various electrolyte concentration, and the impacts of various surface charge were studied by implementing the MPB model with the Si-NW FET biosensor. Additionally, a comparison between the use of the MPB and the Poisson–Boltzmann model in studying the effects of various surface charges was carried out. Taken together, it was found that the MPB model showed a higher resolution in studying the Si-NW FET biosensor model when higher concentrations and surface charges were administered.     

Accurate modeling of the intramolecular electrostatic energy of proteins

The (?, ψ) energy surface of blocked alanine (N-acetyl–N′-methyl alanineamide) was calculated at the Hartree-Fock (HF)/6-31G* level using ab initio molecular orbital theory. A collection of six electrostatic models was constructed, and the term electrostatic model was used to refer to (1) a set of atomic charge densities, each unable to deform with conformation; and (2) a rule for estimating the electrostatic interaction energy between a pair of atomic charge densities. In addition to two partial charge and three multipole electrostatic models, this collection includes one extremely detailed model, which we refer to as nonspherical CPK. For each of these six electrostatic models, parameters—in the form of partial charges, atomic multipoles, or generalized atomic densities—were calculated from the HF/6-31G* wave functions whose energies define the ab initio energy surface. This calculation of parameters was complicated by a problem that was found to originate from the locking in of a set of atomic charge densities, each of which contains a small polarization-induced deformation from its idealized unpolarized state. It was observed that the collective contribution of these small polarization-induced deformations to electrostatic energy differences between conformations can become large relative to ab initio energy differences between conformations. For each of the six electrostatic models, this contribution was reduced by an averaging of atomic charge densities (or electrostatic energy surfaces) over a large collection of conformations. The ab initio energy surface was used as a target with respect to which relative accuracies were determined for the six electrostatic models. A collection of 42 more complete molecular mechanics models was created by combining each of our six electrostatic models with a collection of seven models of repulsion + dispersion + intrinsic torsional energy, chosen to provide a representative sample of functional forms and parameter sets. A measure of distance was defined between model and ab initio energy surfaces; and distances were calculated for each of our 42 molecular mechanics models. For most of our 12 standard molecular mechanics models, the average error between model and ab initio energy surfaces is greater than 1.5 kcal/mol. This error is decreased by (1) careful treatment of the nonspherical nature of atomic charge densities, and (2) accurate representation of electrostatic interaction energies of types 1—2 and 1—3. This result suggests an electrostatic origin for at least part of the error between standard model and ab initio energy surfaces. Given the range of functional forms that is used by the current generation of protein potential functions, these errors cannot be corrected by compensating for errors in other energy components. © 1995 by John Wiley & Sons, Inc.     

Modeling the surface charge evolution of spherical nanoparticles by considering dielectric discontinuity effects at the solid/electrolyte solution interface

It is well known that the electrostatic repulsions between charges on neighboring sites decrease the effective charge at the surface of a charged nanoparticle (NP). However, the situation is more complex close to a dielectric discontinuity, since charged sites are interacting not only with their neighbors but also with their own image charges and the image charges of all neighbors. Titrating site positions, solution ionic concentration, dielectric discontinuity effects, and surface charge variations with pH are investigated here using a grand canonical Monte Carlo method. A Tanford and Kirkwood approach is used to calculate the interaction potentials between the discrete charged sites. Homogeneous, heterogeneous, and patch site distributions are considered to reproduce the various titrating site distributions at the solid/solution interface of spherical NPs. By considering Coulomb, salt, and image charges effects, results show that for different ionic concentrations, modifications of the dielectric constant of NPs having homogeneous and heterogeneous site distributions have little effect on their charging process. Thus, the reaction field, due to the presence of image charges, fully counterbalances the Coulomb interactions. This is not the case for patch distributions, where Coulomb interactions are not completely counterbalanced by the reaction field. Application of the present model to pyrogenic silica is also performed and comparison is made with published experimental data of titration curves at various ionic concentrations.     

Size and shape dependence of the electrostatic potential in cluster models of the MgO(100) surface

We investigated the dependence of the electrostatic potential on the size and the shape of various cluster models of the MgO(100) surface. Both Mg²⁺ and O²⁻ adsorption sites have been considered. The clusters were embedded in a large array of point charges to provide a representation of the Madelung potential. We found that the electrostatic potential in the adsorption region shows a marked dependence on the size of the cluster, in particular, for non-stoichiometric clusters where the number of cations and anions differs considerably. These oscillations are due to (a) the different contribution to the electrostatic potential given by a point charge or by an extended ion, and (b) by the polarization of the ions at the cluster border. The effect of the oscillations in the electrostatic potential on the chemisorption properties was investigated for the case of CO₂ interacting with surface and defect O²⁻ sites of the MgO surface. © 1996 John Wiley & Sons, Inc.     

Three‐Component Langmuir–Blodgett Films Consisting of Surfactant,Clay Mineral,and Lysozyme: Construction and Characterization

The Langmuir–Blodgett (L–B) technique has been employed for the construction of hybrid films consisting of three components: surfactant, clay, and lysozyme (Lys). The surfactants are octadecylammonium chloride (ODAH) and octadecyl ester of rhodamine B (RhB18). The clays include saponite and laponite. Surface pressure versus area isotherms indicate that lysozyme is adsorbed by the surfactant–clay L–B film at the air–water interface without phase transition. The UV‐visible spectra of the hybrid film ODAH–saponite–Lys show that the amount of immobilized lysozyme in the hybrid film is (1.3±0.2) ng mm^?2. The average surface area (Ω) per molecule of lysozyme is approximately 18.2 nm² in the saponite layer. For the multilayer film (ODAH–saponite–Lys)_n, the average amount of lysozyme per layer is (1.0±0.1) ng mm^?2. The amount of lysozyme found in the hybrid films of ODAH–laponite–Lys is at the detection limit of about 0.4 ng mm^?2. Attenuated total reflectance (ATR) FTIR spectra give evidence for clay layers, ODAH, lysozyme, and water in the hybrid film. The octadecylammonium cations are partially oxidized to the corresponding carbamate. A weak 1620 cm^?1 band of lysozyme in the hybrid films is reminiscent of the presence of lysozyme aggregates. AFM reveals evidence of randomly oriented saponite layers of various sizes and shapes. Individual lysozyme molecules are not resolved, but aggregates of about 20 nm in diameter are clearly seen. Some aggregates are in contact with the clay mineral layers, others are not. These aggregates are aligned in films deposited at a surface pressure of 20 mN m^?1.     

Effective atomic charges in alanine dipeptide

A new set of effective atomic charges of different conformers of alanine dipeptide is presented. These charges are obtained by fitting the electrostatic potential resulting from the ab initio SCF wave function of the system obtained in a 6-31G basis set. A specific fit procedure is used providing charges weakly dependent on the fit points as well as on the geometry of the molecule. It is shown that these charges retain a reasonable chemical meaning. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 473–482, 1999     

Base stacking in cytosine dimer. A comparison of correlated ab initio calculations with three empirical potential models and density functional theory calculations

Ab initio MP2/6-31G* interaction energies were calculated for more than 80 geometries of stacked cytosine dimer. Diffuse polarization functions were used to properly cover the dispersion energy. The results of ab initio calculations were compared with those obtained from three electrostatic empirical potential models, constructed as the sum of a Lennard-Jones potential (covering dispersion and repulsion contributions) and the electrostatic term. Point charges and point multipoles of the electrostatic term were also obtained at the MP2/6-31G* level of theory. The point charge MEP model (atomic charges derived from molecular electrostatic potential) satisfactorily reproduced the ab initio data. Addition of π-charges localized below and above the cytosine plane did not affect the calculated energies. The model employing the distributed multipole analysis gave worse agreement with the ab initio data than the MEP approach. The MP2 MEP charges were also derived using larger sets of atomic orbitals: cc-pVDZ, 6-311 + G(2d, p), and aug-cc-pVDZ. Differences between interaction energies calculated using these three sets of point charges and the MP2/6-31G* charges were smaller than 0.8 kcal/mol. The correlated ab initio calculations were also compared with the density functional theory (DFT) method. DFT calculations well reproduced the electrostatic part of interaction energy. They also covered some nonelectrostatic short-range effects which were not reproduced by the empirical potentials. The DFT method does not include the dispersion energy. This energy, approximated by an empirical term, was therefore added to the DFT interaction energy. The resulting interaction energy exhibited an artifact secondary minimum for a 3.9-4.0 vertical separation of bases. This defect is inherent in the DFT functionals, because it is not observed for the Hartree-Fock + dispersion interaction energy.© 1996 John Wiley & Sons, Inc.     

Accurate partial atomic charges for high-energy molecules using class IV charge models with the MIDI! basis set

We have recently developed a new class IV charge model for calculating partial atomic charges in molecules. The new model, called charge model 3 (CM3), was parameterized for calculations on molecules containing H, Li, C, N, O, F, Si, S, P, Cl, and Br by Hartree–Fock theory and by hybrid density functional theory (HDFT) based on the modified Perdew–Wang density functional with several basis sets. In the present article, we extend CM3 for calculating partial atomic charges by Hartree–Fock theory with the economical but well balanced MIDI! basis set. Then, using a test set of accurate dipole moments for molecules containing nitramine functional groups (which include many high-energy materials), we demonstrate the utility of several parameters designed to improve the charges in molecules containing both N and O atoms. We also show that one of our most recently developed CM3 models that is designed for use with wave functions calculated at the mPWXPW91/MIDI! level of theory (where X denotes a variable percentage of Hartree–Fock exchange) gives accurate charge distributions in nitramines without additional parameters for N and O. To demonstrate the reliability of partial atomic charges calculated with CM3, we use these atomic charges to calculate polarization free energies for several nitramines, including the commonly used explosives 1,3,5-trinitro-s-triazine (RDX) and 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane (HNIW), in nitromethane. These polarization energies are large and negative, indicating that electrostatic interactions between the charge distribution of the molecule and the solvent make a large contribution to the free energy of solvation of nitramines. By extension, the same conclusion should apply to solid-state condensation. Also, in contrast to some other charge models, CM3 yields atomic charges that are relatively insensitive to the presence of buried atoms and small conformational changes in the molecule, as well as to the level of treatment of electron correlation. This type of charge model should be useful in the future development of solvation models and force fields designed to estimate intramolecular interactions of nitramines in the condensed phase.     

Intrinsic Surface Reaction Constant in 1-pK Model of Mg-Fe Hydrotalcite-like Compounds

The relationship among intrinsic surface reaction constant (K) in 1-pK model, point of zero net charge (PZNC) and structural charge density (σst) for amphoteric solid with structural charges was established in order to investigate the effect of σst on pK. The theoretical analysis based on 1-pK model indicates that the independent PZNC of electrolyte concentration (c) exists for amphoteric solid with structural charges. A common intersection point (CIP) should appear on the acid-base titration curves at different c, and the pH at the CIP is pHPZNC. The pK can be expressed as pK=-pHPZNC log[(1 2αPZNC)/(1-2αPZNC)], where αPZNC≡σst/eNANs, in which e is the elementary charge, NA the Avogadro‘s constant and Ns the total density of surface sites. For solids without structural charges, pK=-pHPZNC. The pK values of hydrotalcite-like compounds (HTlc) with general formula of [Mg1-xFex(OH)2](Cl,OH)x were evaluated. With increasing x, the pK increases, which can be explained based on the affinity of metal cations for H^- or OH^- and the electrostatic interaction between charging surface and H^- or OH^-.     

Consensus bond-charge increments fitted to electrostatic potential or field of many compounds: Application to MMFF94 training set

Bond-charge increments (BCIs) are additive parameters used to assign atomic charges for the MMFF force field. BCI parameters are classified parsimoniously according to two atom types and the bond order. We show how BCIs may be fitted rapidly by linear least squares to the calculated ab initio electrostatic potential (ESP) or to the electrostatic field. When applied simultaneously to a set of compounds or conformations, the method yields consensus values of the BCIs. The method can also derive conventional “ESP-fit” atomic charges with improved numerical stability. The method may be generalized to determine atom multipoles, multicenter charge templates, or electronegativities, but not polarizability or hardness. We determine 65 potential-derived (PD) BCI parameters, which are classified as in MMFF, by fitting the 6-31G* ESP or the electrostatic field of the 45 compounds in the original MMFF94 training set. We compare the consensus BCIs with classified BCIs that were fit to each molecule individually and with “unique-bond” BCIs (ESP-derived atom charges). Consensus BCIs give a satisfactory representation for about half of the structures and are robust to the adjustment of the alkyl CH bond increment to the zero value employed in MMFF94. We highlight problems at three levels: Point approximation: the potential near lone pairs on sulfur and to some extent nitrogen cannot be represented just by atom charges. Bond classification: BCIs classified according to MMFF atom types cannot represent all delocalized electronic effects. The problem is especially severe for bonds between atoms of equivalent MMFF type, whose BCI must be taken as zero. Consensus: discrepancies that occur in forming the consensus across the training set indicate the need for a more detailed classification of BCIs. Contradictions are seen (e.g., between acetic acid and acetone and between guanidine and formaldehydeimine). We then test the three sets of PD-BCIs in energy minimizations of hydrogen-bonded dimers. Unique-bond BCIs used with the MMFF buffered 14–7 potential reproduce unscaled quantum chemical dimer interaction energies within 0.9 kcal/mol root mean square (or 0.5, omitting two N-oxides). These energies are on average 0.7 (or 0.5) kcal/mol too weak to reproduce the scaled quantum mechanical (SQM) results that are a benchmark for MMFF parameterization. Consensus BCIs tend to weaken the dimer energy by a further 0.4–0.6 kcal/mol. Thus, consensus PD-BCIs can serve as a starting point for MMFF parameterization, but they require both systematic and individual adjustments. Used with a “harder” AMBER-like Lennard–Jones potential, unique-bond PD-BCIs without systematic adjustment give dimer energies in fairly good agreement with SQM. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1495–1516, 1999     

Hyperelectronic polarization in macromolecular solids

Hyperelectronic polarization may be viewed as the electrical polarization in external fields due to the pliant interaction with the charge pairs of excitons, in which the charges are molecularly separated and range over molecularly limited domains. It is particularly pronounced in molecular solids composed of long polymeric molecules having extensive regions of electronic orbital delocalization. Hyperelectronic polarization is regarded as the principal contributor to the high polarizabilities of the following five macromolecular solids: four polyacene quinone radical polymers formed by condensation of aromatic hydrocarbon derivatives with aromatic acids and poly(Cu(II)-N,N′- dimethyl rebeanate). The first four polymers at 100 hz had dielectric constants of 1800–2400, decreasing to about 58–100 at 100,000 hz, with relaxation times of 10^?3 to 10^?4 sec. A sixth polymer, a Schiff-base condensate of 1,4-napthaquinone and p-toluene diisocyanate, however, showed little hyperelectronic polarization, displaying a dielectric constant of 10, constant over 100–100,000 hz. By simple arguments it is shown that the relaxation times and the frequency response of conduction are consonant with the proposed model of charges roaming over long molecular domains (up to 4000 A.) but restricted by molecular boundaries.