Zhong-Zhi Yang

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.

Investigation of the regio- and stereoselectivity of Diels-Alder reactions by newly developed abeem σπ model on the basis of local HSAB principle and maximum hardness principle

Abstract On the basis of density functional theory, a scheme for efficient calculating Fukui function, local softness, and hardness within atom-bond electronegativity equalization method plus σπ model is delivered. By the local softness obtained through this model, we investigated the regioselectivity of Diels–Alder reaction in light of local HSAB principle, and the result is in accordance with experimental and theoretical results. Moreover, we demonstrate for the first time that the maximum hardness principle is obeyed in the stereospecific Diels–Alder reactions, i.e., compared with exo isomer, the more stable endo isomer usually has larger hardness value, consequently, composes the main product.

A characteristic molecular contour evaluated by a theoretical method

Abstract The potential Vα(r1) acting on an α-spin electron at position r1 in a molecule is expressed and then calculated using an ab initio quantum chemical program. An intrinsic characteristic contour of a molecule is defined by those points R where the equation V α ( R )=−I is observed, in which I is the first ionization potential of the molecule. This implies that the molecular contour represents the classical turning surface for the electronic motion within the molecule. A few examples are shown and discussed.

Uniqueness and asymptotic behavior of the local kinetic energy

The exact asymptotic behavior and the uniqueness of the local kinetic energy are discussed. The physical significance of the local kinetic energy is demonstrated, and a few popular models of the local kinetic energy are surveyed and compared.

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.

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.

Study on properties of liquid ammonia via molecular dynamics simulation based on ABEEMσπ polarisable force field

Abstract The molecular dynamics simulation has been performed to investigate the charge distribution, structural and dynamical properties of liquid ammonia at 273 K using a polarisable force field of the atom-bond electronegativity equalisation method (ABEEMσπ). One ammonia molecule in this model has eight charge sites, one N atomic site, three H atomic sites, three N–H bond sites and one lone-pair electron site. ABEEMσπ model can present the quantitative site charges of molecular ammonias in liquid and their changing in response to their surroundings. The radial distribution functions and dynamical properties are in fair agreement with the available experimental data. The first peak of gNN(r) appears at N–N distance of ~3.50 ± 0.05 Å where most hydrogen bonds are formed. The average coordination number of the first shell is 13.0 ± 0.1 among which a central ammonia molecule intimately connects 3 ~ 4 ammonia molecules by hydrogen bonds. The power spectrum shows the vibrations of hydrogen bonds. For a reference, a simple estimation of the average hydrogen bonding energy in liquid ammonia is 6.5 ± 0.1 kcal/mol larger than 3.8 ± 0.3 kcal/mol in dimer ammonia. Our simulation results provide more detailed information about liquid ammonia.

Studies on Hydrolysis Mechanism of Anticancer Ruthenium Drug ImH[ trans -Ru(Im) 2 Cl 4 ] via ABEEM σπ Polarizable Force Field Combined with QM and MD-FEP

We used ABEEMσπ(atom-bond electronegativity equalization method) polarizable force field(ABEEMσπ PFF) method combined with QM and molecular dynamics-free energy perturbation(MD-FEP) methods to investigate the function of water molecules in hydrolysis process of ImH[trans-Ru(Im)2Cl4](ICR). The activation free energies obtained via MD-FEP calculation are in fair agreement with the experimental data. In addition, QM/MM(ABEEM) rationally describes the charge distributions and the electrostatic interaction between molecules. ABEEMσπ fluctuating charge model has the following good characteristics: (1) not only atomic charge regions but also σ, π bond and lone pair charge regions are explicitly represented for a molecule; (2) the region charges are geometry dependent and calculated from time to time in the dynamic simulation without any iterative procedure so that its performance is time-saving compared with the Drude model and induced dipole model.

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 that 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 O-O 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 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.