ABEEM/MM OH- Models for OH-(H2O)n Clusters and Aqueous OH-: Structures, Charge Distributions, and Binding Energies.

Based on the atom-bond electronegativity equalization method fused into molecular mechanics (ABEEM/MM), two fluctuating charge models of OH--water system were proposed. The difference between these two models is whether there is charge transfer between OH- and its first-shell water molecules. The structures, charge distributions, charge transfer, and binding energies of the OH-(H2O)n (n = 1-8, 10, 15, 23) clusters were studied by these two ABEEM/MM models, the OPLS/AA force field, the OPLS-SMOOTH/AA force field, and the QM methods. The results demonstrate that two ABEEM/MM models can search out all stable structures just as the QM methods, and the structures and charge distributions agree well with those from the QM calculations. The structures, the charge transfer, and the strength of hydrogen bonds in the first hydration shell are closely related to the coordination number of OH-. Molecular dynamics simulations on the aqueous OH- solution are performed at 298 and 278 K using ABEEM/MM-I model. The MD results show that the populations of three-, four-, and five-coordinated OH- are 29.6%, 67.1%, and 3.4% at 298 K, respectively, and those of two-, three-, four-, and five-coordinated OH- are 10.8%, 44.9%, 39.2%, and 4.9% at 278 K, respectively; the average hydrogen bond lengths and the hydrogen bond angle in the first shell increase with the temperature decreasing.

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

Nitrosylation reaction mechanisms of the hydrolysates of NAMI-A and hydrolysis reactions of ruthenium nitrosyl complexes were investigated in the triplet state and the singlet state. Activation free energies were calculated by combining the QM/MM(ABEEM) method with free energy perturbation theory, and the explicit solvent environment was simulated by an ABEEMσπ polarizable force field. Our results demonstrate that nitrosylation reactions of the hydrolysates of NAMI-A occur in both the triplet and the singlet states. The Ru-N-O angle of the triplet ruthenium nitrosyl complexes is in the range of 132.0°-138.2°. However, all the ruthenium nitrosyl complexes at the singlet state show an almost linear Ru-N-O angle. The nitrosylation reaction happens prior to the hydrolysis reaction for the first-step hydrolysates. The activation free energies of the nitrosylation reactions show that the H2 O-NO exchange reaction of [RuCl4 (Im)(H2 O)] in the singlet spin sate is the most likely one. Comparing with the activation free energies of the hydrolysis reactions of the ruthenium nitrosyl complexes, the results indicate that the rate of the DMSO-H2 O exchange reaction of [RuCl3 (NO)(Im)(DMSO)] is faster than that of [RuCl3 (H2 O)(Im)(DMSO)] in both the triplet spin state and the singlet spin state. © 2018 Wiley Periodicals, Inc.

Theoretical reflections on the structural polymorphism of the oxygen-evolving complex in the S2 state and the correlations to substrate water exchange and water oxidation mechanism in photosynthesis.

The structural polymorphism of the oxygen-evolving complex is of great significance to photosynthetic water oxidation. Employing density functional theory calculations, we have made further advisement on the interconversion mechanism of O5 transfer in the S2 state, mainly focusing on the potentiality of multi-state reactivity and spin transitions. Then, O5 protonation is proven impossible in S2 for irreversibility of the interconversion, which serves as an auxiliary judgment for the protonation state of O5 in S1. Besides, the structural polymorphism could also be archived by alternative mechanisms involving Mn3 ligand exchange, one of which with Mn3(III) makes sense to substrate water exchange in S2, although being irresponsible for the derivations of the observed EPR signals. During the water exchange, high-spin states would prevail to facilitate electron transfer between the ferromagnetically coupled Mn centers. In addition, water exchange in S1 could account for the closed-cubane structure as the initial form entering S2 at cryogenic temperatures. With regard to water oxidation, the structural flexibility and variability in both S2 and S3 guarantee smooth W2-O5 coupling in S4, according to the substrate assignments from water exchange kinetics. Within this theoretical framework, the new XFEL findings on S1-S3 can be readily rationalized. Finally, an alternative mechanistic scenario for OO bond formation with ·OH radical near O4 is presented, followed by water binding to the pivot Mn4(III) from O4 side during S4-S0. This may diversify the substrate sources combined with the Ca channel in water delivery for the forthcoming S-cycle.

The open-cubane oxo-oxyl coupling mechanism dominates photosynthetic oxygen evolution: a comprehensive DFT investigation on O-O bond formation in the S4 state.

The dioxygen formation mechanism of biological water oxidation in nature has long been the focus of argument; many diverse mechanistic hypotheses have been proposed. Based on a recent breakthrough in the resolution of the electronic and structural properties of the oxygen-evolving complex in the S3 state, our density functional theory (DFT) calculations reveal that the open-cubane oxo-oxyl coupling mechanism, whose substrates preferably originate from W2 and O5 in the S2 state, emerges as the best candidate for O-O bond formation in the S4 state. This is justified by the overwhelming energetic superiority of this mechanism over alternative mechanisms in both the isomeric open and closed-cubane forms of the Mn4CaO5 cluster; spin-dependent reactivity rooted in variable magnetic couplings was found to play an essential role. Importantly, this oxygen evolution mechanism is supported by the recent discovery of femtosecond X-ray free electron lasers (XFEL), and the origin of the observed structural changes from the S1 to S3 state has been analyzed. In this view, we corroborate the proposed water binding mechanism during S2-S3 transition and correlate the theoretical models with experimental findings from aspects of substrate selectivity according to water exchange kinetics. This theoretical consequence for native metalloenzymes may serve as a significant guide for improving the design and synthesis of biomimetic materials in the field of photocatalytic water splitting.

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

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 kHB 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.

How does ammonia bind to the oxygen-evolving complex in the S2 state of photosynthetic water oxidation? Theoretical support and implications for the W1 substitution mechanism.

Ammonia as a water analogue can bind to the Mn4CaO5 cluster of the oxygen-evolving complex in concomitance with ligand substitution and underlying structural transformation. On account of current controversies of the binding site and the absence of the viewpoint of reactivity and mechanistic proofs, we have investigated three modes of NH3 binding based on our elaborations of the possible reaction mechanisms, in correspondence with experimental observation for the NH3-altered g ≈ 2.0 EPR multiline signal. Broken-symmetry density functional theory was employed to construct all the spin surfaces. As a result, we rule out the O5 substitution strategy owing to the impenetrable free energy barrier exceeding 30 kcal mol-1, and alternative routes to destroy the O5 bridge are also blocked. The W1 substitution mechanism is shown to be quite facile, with the barrier not above 11.4 kcal mol-1. For the Mn4 addition scheme, the 'redox switch mechanism' was not implemented by our model, and the effective ways found render 15-22 kcal mol-1 energetic disadvantage by contrast. Consequently, it is strongly in favor of the W1 substitution mechanism for its overwhelming superiority in reactivity, reaching a consensus with the new pulse EPR conclusion. Then, we point out that ammonia departure occurs in the S4' state, with the O-O bonding but unreleased molecular O2. In the meantime, we propose two alternative channels for water binding in the S0' state and expound the significance to substrate selectivity. Ultimately, implications for the mechanism of O-O bond formation are discussed and all the remaining options are listed for future explorations.

Calculating solvation energies by means of a fluctuating charge model combined with continuum solvent model.

Continuum solvent models have shown to be very efficient for calculating solvation energy of biomolecules in solution. However, in order to produce accurate results, besides atomic radii or volumes, an appropriate set of partial charges of the molecule is needed. Here, a set of partial charges produced by a fluctuating charge model-the atom-bond electronegativity equalization method model (ABEEMσπ) fused into molecular mechanics is used to fit for the analytical continuum electrostatics model of generalized-Born calculations. Because the partial atomic charges provided by the ABEEMσπ model can well reflect the polarization effect of the solute induced by the continuum solvent in solution, accurate and rapid calculations of the solvation energies have been performed for series of compounds involving 105 small neutral molecules, twenty kinds of dipeptides and several protein fragments. The solvation energies of small neutral molecules computed with the combination of the GB model with the fluctuating charge protocol (ABEEMσπ∕GB) show remarkable agreement with the experimental results, with a correlation coefficient of 0.97, a slope of 0.95, and a bias of 0.34 kcal∕mol. Furthermore, for twenty kinds of dipeptides and several protein fragments, the results obtained from the analytical ABEEMσπ∕GB model calculations correlate well with those from ab initio and Poisson-Boltzmann calculations. The remarkable agreement between the solvation energies computed with the ABEEMσπ∕GB model and PB model provides strong motivation for the use of ABEEMσπ∕GB solvent model in the simulation of biochemical systems.

Investigation of the molecular surface area and volume: Defined and calculated by the molecular face theory.

Based on the molecular face (MF) theory, the molecular face surface area (MFSA) and molecular face volume (MFV) are defined. For a variety of organic molecules and several inorganic molecules, the MFSA and MFV have been studied and calculated in terms of an algorithm of our own via the Matlab package. The MFV shows a very good linear relationship with the experimentally measured critical molar volume. It is also found that the MFSA and MFV have significant linear correlations with those of the commonly used hard-sphere model and the electron density isosurface.

Development of a Polarizable Force Field Using Multiple Fluctuating Charges per Atom.

A polarizable force field (PFF) using multiple fluctuating charges per atom, ABEEMσπ PFF, is presented in this work. The fluctuating partial charges are obtained from the electronegativity equalization principle applied to the decomposition scheme of atom-bond regions into multiple charge sites: atomic, lone-pair electron, and σ and π bond regions. These multiple partial charges per atom should better account for the polarization effect than single atomic charge in other PFFs. To evaluate the PFF, structural and energetic properties for some organic and biochemical systems, including rotational barriers; binding energies of base pairs; a base-base interaction in a B-DNA decamer; and interaction energies of ten stationary conformers of a water dimer, peptides, and bases with water molecules, have been calculated and compared with the experimental data or ab initio MP2 results. Molecular dynamics simulations using the PFF have been performed for crambin and BPTI protein systems. Better performances in modeling root-mean-square deviations of backbone bond lengths, bond angles, key dihedral angles, the coordinate root-mean-square shift of atoms, and the distribution of hydrogen bonds have been observed in comparison with other PFFs. These results indicate that the fluctuating charge force field, ABEEMσπ/MM, is accurate and reliable and can be applied to wide ranges of organic and biomolecular systems.

Insight into mechanism of formation of c8 adducts in carcinogenic reactions of arylnitrenium ions with purine nucleosides.

For the most important arylnitrenium ion-guanosine C8 adducts in the reactions involving arylamine-initiated carcinogenesis, a detailed mechanism of their formation still remains unclear. In this paper, we employ quantum chemistry methods to explore this issue. Our study indicates that formation of these C8 adducts proceeds directly by additions of arylnitrenium ions to C8 position of nucleoside bases in DNA. The good agreements of theoretical rate constants, pK(a) value, and NMR chemical shifts of C8 intermediate with experimental data support this theoretical finding. Excitingly, predictions of what adducts can be observed in reactions of arylnitrenium ions with guanine and hypoxanthine are in fair agreement with experimental observations. This study answers an important question, in carcinogenesis researches, of what is the mechanism for formation of C8 adducts.

The relations of bond length and force constant with the potential acting on an electron in a molecule.

Within a molecule, the potential acting on an electron (PAEM) is defined as the interaction energy of a local electron with the rest of the particles, i.e., all nuclei and remaining electrons. The formalism of the PAEM is first derived, and the calculated PAEMs are then obtained by using the ab initio program based on the MELD program package for a series of diatomic halides, namely, HX, LiX, NaX, and X(2) molecules (X= F, Cl, Br, and I), as well as H(2)O and NH(3), and some organic molecules. By comparing the 3D topological graphs of the PAEMs, we found that there is a saddle point along every chemical bond axis. Further, the good linear correlations of the force constant and bond length with the PAEMs are explored through a definition of D(pb), which is the absolute value (i.e., the negative) of the PAEM at the saddle point along the chemical bond axis. In addition, the difference between the PAEM and molecular electrostatic potential (MEP) is pointed out by analyzing both their definitions and numerical results.

Method and algorithm of obtaining the molecular intrinsic characteristic contours (MICCs) of organic molecules.

The molecular intrinsic characteristic contour (MICC) is defined as the set of all the classical turning points of electron movement in a molecule. Studies on the MICCs of some medium organic molecules, such as dimethylether, acetone, and some homologues of alkanes, alkenes, and alkynes, as well as the electron density distributions on the MICCs, are shown for the first time. Results show that the MICC is an intrinsic approach to shape and size of a molecule. Unlike the van der Waals hard-sphere model, the MICC is a smooth contour, and it has a clear physical meaning. Detailed investigations on the cross-sections of MICCs have provided a kind of important information about atomic size changing in the process of forming molecules. Studies on electron density distribution on the MICC not only provide a new insight into molecular shape, but also show that the electron density distribution on the boundary surface relates closely with molecular properties and reactivities. For the homologues of alkanes, Rout(H), Dmin, and Dmax (the minimum and maximum of electron density on the MICC), all have very good linear relationships with minus of the molecular ionization potential. This work may serve as a basis for exploring a new reactivity indicator of chemical reactions and for studying molecular shape properties of large organic and biological molecules.