Solvation free energies calculated using the GB/SA model: Sensitivity of results on charge sets,protocols, and force fields

The sensitivity of aqueous solvation free energies (SFEs), estimated using the GB/SA continuum solvent model, on charge sets, protocols, and force fields, was studied. Simple energy calculations using the GB/SA solvent model were performed on 11 monofunctional organic compounds. Results indicate that calculated SFEs are strongly dependent on the charge sets. Charges derived from electrostatic potential fitting to high level ab initio wave functions using the CHELPG procedure and “class IV” charges from AM1/CM1a or PM3/CM1p calculations yielded better results than the corresponding Mulliken charges. Calculated SFEs were similar to MC/FEP energies obtained in the presence of explicit TIP4P water. Further improvements were obtained by using GVB/6-31G** and MP2/6-31+G** (CHELPG) charge sets that included correlation effects. SFEs calculated using charge sets assigned by the OPLSA* force field gave the best results of all standard force fields (MM2*, MM3*, MMFF, AMBER*, and OPLSA*) implemented in MacroModel. Comparison of relative and absolute SFEs computed using either the GB/SA continuum model or MC/FEP calculations in the presence of explicit TIP4P water showed that, in general, relative SFEs can be estimated with greater accuracy. A second set of 20 mono- and difunctional molecules was also studied and relative SFEs estimated using energy minimization and thermodynamic cycle perturbation (TCP) protocols. SFEs calculated from TCP calculations using the GB/SA model were sensitive to bond lengths of dummy bonds (i.e., bonds involving dummy atoms). In such cases, keeping the bond lengths of dummy bonds close to the corresponding bond lengths of the starting structures improved the agreement of TCP-calculated SFEs with energy minimization results. Overall, these results indicate that GB/SA solvation free energy estimates from simple energy minimization calculations are of similar accuracy and value to those obtained using more elaborate TCP protocols. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 769–780, 1998     

Study of water clusters in the n = 2–34 size regime, based on the ABEEM/MM model

Various properties of water clusters in the n = 2–34 size regime with the change of cluster size have been systemically explored based on the newly developed flexible-body and charge-fluctuating ABEEM/MM water potential model. The ABEEM/MM water model is to take ABEEM charges of all atoms, bonds, and lone-pairs of water molecules into the intermolecular electrostatic interaction term in molecular mechanics. The computed correlating properties characterizing water clusters (H₂O) _n (n = 2–34) include optimal structures, structural parameters, ABEEM charge distributions, binding energies, hydrogen bonds, dipole moments, and so on. The study of optimal structures shows that the ABEEM/MM model can correctly predict the following important structural features, such as the transition from two-dimensional (from dimer to pentamer) to three-dimensional (for clusters larger than the hexamer) structures at hexamer region, the transition from cubes to cages at dodecamer (H₂O)₁₂, the transition from all-surface (all water molecules on the surface of the cluster) to one water-centered (one water molecule at the center of the cluster, fully solvated) structures at (H₂O)₁₇, the transition from one to two internal molecules in the cage at (H₂O)₃₃, and so on. The first three structural transitions are in good agreement with those obtained from previous work, while the fourth transition is different from that identified by Hartke. Subsequently, a systematic investigation of structural parameters, ABEEM charges, energetic properties, and dipole moments of water clusters with increasing cluster size can provide important reference for describing the objective trait of hydrogen bonds in water cluster system, and also provide a strong impetus toward understanding how the water clusters approach the bulk limit.     

Analysis of Main Factors Determining the Prediction of Stabilization Energies of Halide-water Clusters

This work studies the main factors determining the stabilization energy [E _stab(n)] of a series of halide clusters, [X(H₂O) _n ]⁻ (X≡F, Br and I). This property measures the difference between the ionization process of the hydrated and isolated halide. In a previous paper [J. Chem. Phys., 121, 7269 (2004)], the E _stab(n) was studied for a large number of clusters (up to n = 60) by using classical computer simulations based on first-principles polarizable potentials to describe the halide–water interactions. In this work we analyze what features of the MCDHO-type model are necessary for a proper reproduction of the experimental E _stab. The role of the charge redistribution (polarizability) of the water molecule and halide anion, the geometrical relaxation of water molecule (flexibility), as well as the replacement of water clusters by a dielectric continuum of different dielectric permittivities are presented and discussed. The parallel behavior of the E _stab magnitude with the dielectric permittivity of the continuum and with the number of water molecules forming the cluster supports that the electrostatic interactions are the main responsible for the changes induced on the electron structures determining the energetics of the photodetachement process. The photodetachment process does not only occur without nuclear relaxation but also with a small electron redistribution of water molecules.     

Effective Charges and Ionicity in Molten Salts

Abstract

We have used experimental values of the entropies, near melting, of molten salts to calculate their effective charges by using a charge a spheres model in the Mean Spherical Approximation (MSA).

We compare the values of the effective charges with the electronegativity differences for a number of 1:1 molten salts. We find a reasonable good correlation for the alkali halides, but no for the copper, silver and thallium halides, and we offer an explanation for these results.     

The investigation on the relative stability of different clusters of thiourea dioxide in water using gas phase quantum chemical calculations

The relative stability of different clusters of thiourea dioxide (TDO) in water is examined using gas phase quantum chemical calculations at the MP2 and B3LYP level with 6‐311++G(d,p) basis set. The possible equilibrium structures and other energetic and geometrical data of the thiourea dioxide clusters, TDO‐(H₂O)_n (n is the number of water molecules), are obtained. The calculation results show that a strong interaction exists between thiourea dioxide and water molecules, as indicated by the binding energies of the TDO clusters progressively increased by adding water molecules. PCM model is used to investigate solvent effect of TDO. We obtained a negative hydration energy of ?20.6 kcal mol^?1 and free‐energy change of ?21.0 kcal mol^?1 in hydration process. On the basis of increasing binding energies with adding water molecules and a negative hydration energy by PCM calculation, we conclude thiourea dioxide can dissolve in water molecules. Furthermore, the increases of the C? S bond distance by the addition of water molecules show that the strength of the C? S bonds is attenuated. We find that when the number of water molecules was up to 5, the C? S bonds of the clusters, TDO‐(H₂O)₅ and TDO‐(H₂O)₆ were ruptured. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009     

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     

A Universal and Straightforward Approach to Include Penetration Effects in Electrostatic Interaction Energy Estimation

To compensate for the lack of the explicit treatment of charge penetration in classical force fields, we propose a new charge‐distribution model based on a promolecule augmented with point charges (aug‐PROmol). It relies on a superposition of spherical atomic electron densities obtained for each chemical element from SCF energy optimized atomic orbitals. Atomic densities are further rescaled by partial point charges computed from fits to the molecular electrostatic potential. Aug‐PROmol was tested on the S66 benchmark dataset extended to nonequilibrium geometries (J. Chem. Theory Comput., 2011, 7, 3466). The model does not need any additional parametrization other than point charges. Despite its simplicity, aug‐PROmol approximates the electrostatic energy with good agreement (RMSE=0.76 kcal mol^?1 to DFT‐SAPT with B3LYP/aug‐cc‐pVTZ).     

Density functional studies of LiN and LiN+ (N = 2–30) clusters: Structure,binding and charge distribution

Density functional calculations using B3LYP/6‐311G method have been carried out for small to medium‐sized lithium clusters (Li_N, N = 2–30). The optimized geometries of neutral and singly charged clusters, their binding energies, ionization potential, electron affinity, chemical potential, softness, hardness, highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO–LUMO) gap, and static dipole polarizability have been investigated systematically. In addition, we study the distribution of partial charges in detail using natural population analysis (NPA) in small‐sized clusters (Li_N, N = 2–10), both neutral and cationic, and demonstrate the correlation between symmetry and charge. Uniform distribution of charges in cationic clusters confirms them to be energetically more favorable than the neutral counterparts. Whenever possible, results have been compared with available data. An excellent agreement in every case supports new results as reliable predictions. A careful study of optimized geometries shows that Li₉ is derivable from bulk Li structure, i.e., body centered cubic cell, and higher clusters have optimized shapes derived from this. Further, the turnover form two to three dimensional structure occurs at cluster size N = 6. The quantity α^1/3 (α = polarizability) per atom is found to be broadly proportional to softness (per atom) as well as inverse ionization potential (per atom). The present work forms a sound basis for further study of large‐sized clusters as well as other atomic clusters. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

Teaching Chemistry with Electron Density Models. 2. Can Atomic Charges Adequately Explain Electrostatic Potential Maps?

Electrostatic potential maps generated from quantum mechanical calculations are widely used to teach students about molecular polarity and assign atomic charges (Shusterman, G. P.; Shusterman, A. J. J. Chem. Educ. 1997, 74, 771–776; Hehre, W. J.; Shusterman, A. J.; Nelson, J. E. The Molecular Modeling Workbook for Organic Chemistry: Wavefunction: Irvine, CA, 1998). The assumption that potential equals charge is only valid, however, when comparing atoms of similar size. The proper use of potential maps requires consideration of atomic charge, atomic radius, and the electron configuration (orbital occupancy) of the atom in question. These points are illustrated through the analysis of the potential maps of various halogen-containing molecules.The first article in this series is Shusterman, G. P.; Shusterman, A. J. J. Chem. Educ. 1997, 74, 771.776.     

Polarization effects on peptide conformations at water–membrane interface by molecular dynamics simulation

The electrostatic image method was applied to investigate the conformation of peptides characterized by different hydrophobicities in a water–membrane interface model. The interface was represented by a surface of discontinuity between two media with different dielectric constants, taking into account the difference between the polarizabilities of the aqueous medium and the hydrocarbon one. The method consists of a substitution of the real problem, which involves the charges and the induced polarization at the surface of discontinuity, by a simpler problem formed with charges and their images. The electric field due to the polarization induced at the surface by charge q was calculated using a hypothetical charge q′ (image of q), symmetrically located on the opposite side of the surface. The value of q′ was determined using the appropriate electrostatic boundary conditions at the surface. By means of this procedure, the effect of the interface can be introduced easily in the usual force field. We included this extension in the computational package that we are developing for molecular dynamics simulations (Thor ). The peptides studied included hydrophilic tetraaspartic acid (Asp–Asp–Asp–Asp), tetralysine (Lys–Lys–Lys–Lys), hydrophobic tetrapeptide (His–Phe–Arg–Trp), an amphiphilic fragment of β-endorphin, and the signal sequence of the E. coli λ-receptor. The simulation results are in agreement with known experimental data regarding the behavior of peptides at the water–membrane interface. An analysis of the conformational dynamics of the signal sequence peptide at the interface was performed over the course of a few nanoseconds. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 971–982, 1999     

Theoretical study of 3d‐metal mononitrides using DFT method

3d‐Metal mononitrides are studied using the density functional theory method. The lowest spin state for these dimers is obtained using the B3LYP hybrid functional with the 6‐311+G* basis set. The equilibrium geometries, vibrational frequencies, binding energies, Mulliken, and natural orbital population analysis charges, natural orbital electronic configuration, electron affinity, and ionization potential are obtained. Mulliken as well as natural orbital population analysis charges indicate that for all dimers, in cations most of the positive charge localized on the transition metal atom where in anions most of the negative charge localized on nitrogen atom. The binding energies for 3d‐metal mononitrides are higher than those for monocarbides and monoxides. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Theory of chemical bonds in metalloenzymes IV: Hybrid‐DFT study of Rieske‐type [2Fe?2S] clusters

The Rieske‐type [2Fe? 2S] cores of electron‐transfer (ET) proteins in the mitochondrial respiratory chain have unusual properties, such as redox potentials and spectroscopy. In this study, part IV of a series, the inherent molecular structures and characteristic electronic structures of the Rieske‐type [2Fe? 2S] clusters are investigated using broken‐symmetry hybrid density functional theory (BS‐HDFT). Geometry optimizations for the oxidized and reduced states were performed and their characteristic vibrational modes are assigned. Magnetic properties are investigated using model Hamiltonians to describe the electron delocalization and the unsymmetric property. The parameters of the model Hamiltonian, such as exchange coupling J, valence delocalization B, and potential energy difference Δ, are evaluated from the BS‐HDFT calculations. The valence localization and excitation energy (ΔE) of the Rieske‐type [2Fe? 2S] cluster are discussed. The chemical bond nature is characterized by chemical indices from natural orbital analysis. Our theoretical results are reasonably consistent with experimental results. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Theoretical study on interactions between thiourea S‐monoxide and water

This work investigated the hydrolyzation of thiourea monoxide using density functional theory (DFT) and Møller–Plesset second‐order (MP2) Theory. We obtained the equilibrium structures and other molecular properties of the clusters. The results show that thiourea monoxide has a good solubility in water solvent, and as indicated, the binding energies of the clusters are increased progressively by the addition of water molecules. Furthermore, the increases of the distance(C? S) and (S? O) by the addition of water molecules indicate that the strength of the C? S and S? O bonds are weakened. When n = 7 (n, the number of water molecules), the C? S bonds of Clusters VII ruptured. We conclude that thiourea monoxide can be decomposed in aqueous solution. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009     

Preliminary results of a theoretical ab initio model study of adsorption on ionic crystals

The adsorption of metals on ionic surfaces takes place on preferential sites and is affected by the presence of defects. In order to provide some theoretical indication concerning electronic energy changes connected with these effects, we have extended previous work [A. Julg and M. Bourg, J. Phys. Lett. 43 , L243 (1982)] where Li_n clusters embedded in a matrix simulated by point charges had been studied by STO -6G (G-70) calculations. We have treated an Li₂ molecule in the presence of an fcc lattice of positive and negative point charges placed at the distances characteristic of an LiF crystal: The perfect surface as well as steps and point defects have been thus simulated. In this article we briefly describe the results obtained.     

Theoretical study on the translocation of partially charged polymers through nanopore

The translocation time τ of partially charged polymers through a neutral nanopore is calculated using Fokker–Planck equation with adsorbing–adsorbing boundary conditions. For the polymer with one charged monomer, we find that τ is dependent on the position of the charged monomer and on the magnitude of the driving force f inside the nanopore. When the charge is located at the front half of the polymer chain, τ is larger than that of neutral polymer and increases with f. When the charge is located at the back half, it is smaller than that of the neutral polymer and decreases with increasing f. We have also studied the behavior of a symmetrical polymer with two like charges located symmetrically in the chain and that of an asymmetrical polymer with two unlike charges. Moreover, we have calculated the translocation time for a general condition of polymer with two randomly distributed charges. All results show that τ is dependent on the positions of charges in the polymer chain and on the magnitude of the driving force. The results can be explained qualitatively by the free‐energy landscape of polymer translocation. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 1017–1025     

Comparative Quantum-Chemical Analysis of the Electronic Structures of the Valence Regions of Active Sites in Cytochromes f and c.

A comparative analysis of densities of states has been carried out for the valence regions of the hemes and clusters of cytochromes f and c using the ZINDO1 semiempirical quantum-chemical method. The molecular orbitals of these structures are formed from the p atomic orbitals of nitrogen and carbon of the porphyrin ring, making equal contributions. For systems with negative charges, more than half of all added electrons are distributed over the porphyrin parts of the molecules. The molecular orbital energies of the valence regions of the corresponding clusters and hemes are nearly the same. In iron porphyrin, as well as in heme f and cytochrome cluster f, the lowest unoccupied molecular orbital is doubly degenerate. In heme c and cytochrome cluster c, the degeneracy is lifted because of the asymmetry of the nearest aminoacid environment and substituents in the porphyrin ring.     

Electrostatic model for infrared intensities in a spectroscopically determined molecular mechanics force field

A new electrostatic model for the calculation of infrared intensities in molecular mechanics and molecular dynamics is presented. The model is based on atomic charges, atomic charge fluxes, and internal coordinate dipoles and their fluxes. The internal coordinate dipoles are used instead of atomic dipoles, thus simplifying the derivation of parameters. The model is designed to reproduce ab initio dipole derivatives, and the parameters can be obtained by (iterative) transformations from these, or by linear least squares fitting to them. A first application to linear alkanes has been made. For these molecules, the intensities can be predicted with an average accuracy of 30–40%. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 754–768, 1998     

A theoretical investigation of the interaction between H,Li, Na,K, and fullerenes

We studied the interaction between H, Li, Na, and K with one and two C₆₀ molecules using unrestricted Hartree–Fock (UHF) methods. We investigated the effects of distances between the doping atoms and the C₆₀ clusters, total charges, interaction energies, stabilities, HOMO‐LUMO energy differences, charge distribution, and potential energy surfaces. The effect of each doping atom was analyzed and potential technological applications discussed. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005