Dong-Xia Zhao

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.

Theoretical Analysis of Gas-Phase Front-Side Attack Identity SN2(C) and SN2(Si) Reactions with Retention of Configuration

Gas-phase front-side attack identity S(N)2(C) and S(N)2(Si) reactions, CH(3)X1 + X2(-) --> CH(3)X2 + X1(-) and SiH(3)X1 + X2(-) --> SiH(3)X2 + X1(-) (X = F, Cl), are investigated by the ab initio method and molecular face (MF) theory. The computations have been performed at the CCSD(T)/aug-cc-pVTZ//MP2/6-311++G(3df,3pd) and CISD/aug-cc-pVDZ levels. Front-side attack identity S(N)2 reactions for both SiH(3)X and CH(3)X have double-well potential energy surfaces (PESs), but their transition-state positions are different relative to the positions of reactants and products: it is lower for SiH(3)X, and it is higher for CH(3)X. The minimum energy path for an S(N)2(Si) reaction with retention of configuration proceeds from a stable pentacoordinated anion intermediate of C(s) symmetry (TBP) via a C(s) transition state (SP) to a complementary pentacoordinated intermediate (TBP) and finally up to separate products. Berry pseudorotation has been observed in the front-side attack identity S(N)2(Si) reactions with F(-) and Cl(-) along the intrinsic reaction coordinate (IRC) routes. In addition, the geometrical transformations of front-side attack identity S(N)2(C) and S(N)2(Si) reactions based on the IRC calculations at the MP2/6-311++G(3df, 3pd) level of theory are described compared with those of corresponding back-side attack reactions. The difference between front-side attack identity S(N)2(C) and S(N)2(Si) reactions has been demonstrated. In MF theory, the potential acting on an electron in a molecule (PAEM) is an important quantity; in particular, its D(pb) can measure the strength of a chemical bond in a molecule. It is found that the difference between D(pb) values of reactant and transition state may be related to the activation energy for front-side and back-side attack S(N)2(C) and S(N)2(Si) reactions, and the D(pb) curves along the IRC routes have features similar to those of the potential energy profiles for all of the back-side attack S(N)2 reactions and front-side attack S(N)2(Si) reaction with F(-). Furthermore, according to the MF theory, the spatial dynamic changing features of the molecular shapes and the face electron density are vividly depicted for the course of the reactions.

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, R  outH , 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.

Theoretical study on characteristic ionic radii

The characteristic radii for univalent cations and anions were defined by the classical turning point of the electron movement in an ion. The numerical results of the elements from firstto third-rows in the periodic table were obtained usingab initio method. The results correlate quite well with Pauling ionic radii and Shannon and Prewitt ionic radii.

The molecular intrinsic characteristic contours (MICCs) of some small organic molecules

A new representation of the molecular intrinsic characteristic contour (MICC) is carried out by using an ab initio method for some small organic molecules, such as methane, ethane, ethylene, acetylene and formaldehyde. The detailed comparison of the MICCs for these molecules with the respective isolated atomic characteristic boundary radii have been done for giving direct information about the spatial change in forming the molecules from individual atoms. These knowledge and related pictures of the potential acting on an electron within a molecule may be useful in discussing the molecular properties and chemical bonding.

THE CHARACTERISTIC BOUNDARY RADII OF ATOMS

The characteristic boundary radius of an atom has been defined as the distance from the classical turning point of electronic motion to the nucleus of the atom. With the ab initio method, the atomic boundary radii for elements from H through Xe are calculated. For the atoms in the same group, the radii defined in this way are of good linear relationship with the empirical radii commonly accepted, such as the van der Waals and covalent atomic radii determined by experimental data.

An estimation method of binding free energy in terms of ABEEMσπ/MM and continuum electrostatics fused into LIE method

A method is proposed for the estimation of absolute binding free energy of interaction between proteins and ligands. The linear interaction energy method is combined with atom‐bond electronegativity equalization method at σπ level Force field (fused into molecular mechanics) and generalized Born continuum model calculation of electrostatic solvation for the estimation of the absolute free energy of binding. The parameters of this method are calibrated by using a training set of 24 HIV‐1 protease–inhibitor complexes (PDB entry 1AAQ). A correlation coefficient of 0.93 was obtained with a root mean square deviation of 0.70 kcal mol−1. This approach is further tested on seven inhibitor and protease complexes, and it provides small root mean square deviation between the calculated binding free energy and experimental binding free energy without reparametrization. By comparing the radii of gyration and the hydrogen bond distances between ligand and protein of three training model molecules, the consistent comparison result of binding free energy is obtained. It proves that this method of calculating the binding free energy with appropriate structural analysis can be applied to quickly assess new inhibitors of HIV‐1 proteases. To test whether the parameters of this method can apply to other drug targets, we have validated this method for the drug target cyclooxygenase‐2.

Valence state parameters of all transition metal atoms in metalloproteins--development of ABEEMσπ fluctuating charge force field.

To promote accuracy of the atom‐bond electronegativity equalization method (ABEEMσπ) fluctuating charge polarizable force fields, and extend it to include all transition metal atoms, a new parameter, the reference charge is set up in the expression of the total energy potential function. We select over 700 model molecules most of which model metalloprotein molecules that come from Protein Data Bank. We set reference charges for different apparent valence states of transition metals and calibrate the parameters of reference charges, valence state electronegativities, and valence state hardnesses for ABEEMσπ through linear regression and least square method. These parameters can be used to calculate charge distributions of metalloproteins containing transition metal atoms (Sc‐Zn, Y‐Cd, and Lu‐Hg). Compared the results of ABEEMσπ charge distributions with those obtained by ab initio method, the quite good linear correlations of the two kinds of charge distributions are shown. The reason why the STO‐3G basis set in Mulliken population analysis for the parameter calibration is specially explained in detail. Furthermore, ABEEMσπ method can also quickly and quite accurately calculate dipole moments of molecules. Molecular dynamics optimizations of five metalloproteins as the examples show that their structures obtained by ABEEMσπ fluctuating charge polarizable force field are very close to the structures optimized by the ab initio MP2/6–311G method. This means that the ABEEMσπ/MM can now be applied to molecular dynamics simulations of systems that contain metalloproteins with good accuracy.

Investigation of the distinction between van der Waals interaction and chemical bonding based on the PAEM-MO diagram

In recent years, the basic problem of understanding chemical bonding, nonbonded, and/or van der Waals interactions has been intensively debated in terms of various theoretical methods. We propose and construct the potential acting on one electron in a molecule‐molecular orbital (PAEM‐MO) diagram, which draws the PAEM inserted the MO energy levels with their major atomic orbital components. PAEM‐MO diagram is able to show clear distinction of chemical bonding from nonbonded and/or vdW interactions. The rule for this is as follows. Along the line connecting two atoms in a molecule or a complex, the existence of chemical bonding between these two atoms needs to satisfy two conditions: (a) a critical point of PAEM exists and (b) PAEM barrier between the two atoms is lower in energy than the occupied major valence‐shell bonding MO which contains in‐phase atomic components (positive overlap) of the two considered atoms. In contrast to the chemical bonding, for a nonbonded interaction or van der Waals interaction between two atoms, both conditions (a) and (b) do not be satisfied at the same time. This is demonstrated and discussed by various typical cases, particularly those related to helium atom and HH bonding in phenanthrene. There are helium bonds in HHeF and HeBeO molecules, whereas no HH bonding in phenanthrene. The validity and limitation for this rule is demonstrated through the investigations of the curves of the PAEM barrier top and MO energies versus the internuclear distances for He2, H2, and He2+ systems.

Molecular intrinsic characteristic contours of small organic molecules containing oxygen atom

By utilizing the classical turning point of the electron movement, we have defined and computed the molecular intrinsic characteristic contour (MICC) via the combination of theab initio quantum chemistry computational method with the ionization potential measured by photoelectron spectroscopy experiment. In this paper, we calculated the MICCs of several small organic molecules containing oxygen atom for the first time. The three-dimensional pictures have been drawn, by performing a large number of calculations. The analysis on some characterized cross-sections of the MICC can provide atomic spatial changing information in the process of forming a molecule.