Journal of Theoretical and Computational Chemistry

The heme activate protein (HAP) is a model system for understanding protein–DNA interactions and allosteric mechanisms in gene regulation. Despite the wealth of biochemical data provided by extensive mutations of HAP, the specific recognition mechanism of the target DNA by HAP has remained elusive. This paper gives the results of a study using molecular dynamics simulations performed for a single DNA fragment (USA_CYC7) and three protein–DNA_CYC7 complex crystal structures: the HAP-wt and two HAP mutants — HAP-PC7: S63G; HAP-18: S63R. Comparative molecular dynamics simulations reveal that the distributions of protein–DNA interactions recognizing the key base steps (CGC) are consistent with their transcriptional activities. Relative to the similar conformations of three bound DNA, the different flexibilities in involving DNA recognition regions: N-term Arm and Zn2Cys6 Binuclear Cluster in three HAPs may result in a variety of protein–DNA recognitions. Despite different intensities of motions, the essential dynamics (ED) analysis shows that the internal motions of three protein–DNA complexes are similar: three proteins all slide along DNA to find their target sites. Thus, under this condition, during the recognition process, the flexibility of the DNA recognizing regions (N-term Arm and Zn2Cys6 Binuclear Cluster regions) plays a crucial role in determining the abilities of protein's recognizing DNA: the higher is its flexibility, the faster it slides along the DNA to find the targeted DNA.

A novel index ED_m based on ionicity index matrix, improved distance matrix, and branching degree matrix is used to describe the structural information of the molecule and realizes unique characterization of the molecular structures. The quantitative structure–property relationship (QSPR) models, with correlation coefficients (R) in the range of 0.99–1.00 for standard enthalpy of formation (), standard entropy (), molar volume (V_m), and molar refraction (R_m) of alkanes, alkenes, and alkynes, are subsequently developed using the index ED_m. The leave-one-out (LOO) method and random sampling prediction (RSP) method demonstrate the models to be statistically significant and reliable. Compared with other published topological descriptors, the index ED_m has many advantages such as zero degeneracy, better simulation, and so on. Furthermore, the models of solubility and octanol–water partition coefficient are built with satisfied results, which further manifests the superiority and wide application of this index.

One- and two-electron nonrelativistic and quasirelativistic basic functions are introduced. The combined analytical relations in terms of these basic functions are derived for the non- and quasi-relativistic atomic integrals over integer and noninteger n-Slater-type orbitals. The relationships obtained are valid for the arbitrary values of principal quantum numbers and screening constants of Slater orbitals.

The inclusion process of β-cyclodextrin (β-CD) with Acetovanillone (Ace) was studied by using PM3 method, and the single-point energy of the inclusion complex was calculated at the level of B3LYP/6-31G*. The calculated data suggest that (1) the inclusion complex formed by Ace entering into the cavity of β-CD from its wide side (the secondary hydroxyl group side) is more stable than that from its narrow side (the primary hydroxyl group side); (2) the formation of the inclusion complex is probably an enthalpy-driven process; (3) the more the charge transfers, the more unstable the inclusion complex is. In addition to the inclusion schemes, other seven interaction schemes of the Ace with β-CD were also investigated and the results suggest that all these schemes should exist in actual experiment.

Thioanalogues of nucleic-acid bases have been shown to be the place of preferential charge or energy localization when incorporated in the system of respective regular bases. Most evidence of such behavior is based on experiments using γ-ray or other ionizing radiation. Here time dependent density functional theory (TDDFT) has been applied to investigate singlet and triplet excited state spectra of thioanalogues and some oxo-derivatives of nucleic-acid bases and compare the spectra to the calculated spectra of the regular bases as well as to the existing experimental data. It has been shown that thioanalogues have lower excitation singlet and triplet energies than are the respective energies in the regular bases. Energy localization on thioanalogues and their spectroscopic properties are related to the effect of sulfur substitution in such systems.

The electronic band structure, density of states, structural phase transition, and superconducting transition temperature under normal and high pressures are reported for titanium (Ti). The normal pressure band structure and density of states of hcp-Ti agree well with the previous calculations. The high pressure band structure exhibits significant deviations from the normal pressure band structure due to s, p → d transition. On the basis of band structure and total energy results obtained using full potential linear muffin-tin orbital method (FP LMTO), we predict a phase transformation sequence of α (hcp) → ω (hexagonal) → γ (distorted hcp) → β (bcc) in titanium under pressure. From our analysis we predict a δ (distorted bcc) phase which is not stable at any high pressures. According to the present calculation, at normal pressure, the superconducting transition of hcp-Ti occurs at 0.36 K which is in agreement with the experimental observation of 0.4 K. When the pressure is increased, it is predicted that, T_c increases at a rate of 3.123 K/Mbar in hcp-Ti. On further increase of pressure T_c begins to decrease at a rate of 1.464 K/Mbar.

The reaction path is an important concept of theoretical chemistry. We use a definition with a reduced gradient (see Quapp et al., Theor Chem Acc100:285, 1998), also named Newton trajectory (NT). To follow a reaction path, we design a numerical scheme for a method for finding a transition state between reactant and product on the potential energy surface: the growing string (GS) method. We extend the method (see W. Quapp, J Chem Phys122:174106, 2005) by a second-order scheme for the corrector step, which includes the use of the Hessian matrix. A dramatic performance enhancement for the exactness to follow the NTs, and a dramatic reduction of the number of corrector steps are to report. Hence, we can calculate flows of NTs. The method works in nonredundant internal coordinates. The corresponding metric to work with is curvilinear. The GS calculation is interfaced with the GamessUS package (we have provided this algorithm on ). Examples for applications are the HCN isomerization pathway and NTs for the isomerization C7ax ↔ C5 of alanine dipeptide.

The complex potential energy surface for the self-reaction of CH₂ClO₂ radicals, including 12 intermediates, 33 interconversion transition states, and 21 major dissociation products, was theoretically probed at the CCSD(T)/cc-pVDZ//B3LYP/6-311G(2d,2p) level of theory. The geometries and relative energies for various stationary points were determined. Based on the calculated CCSD(T)/cc-pVDZ potential energy surface, the possible mechanism for the studied system was proposed. It is shown that the most feasible channels are those leading to 2²CH₂ClO + ³O₂, ²CH₂ClO + ²HO₂ + CHClO, ²CH₂ClO + HCl + ²CH(O)O₂, ²CH₂ClO + ³O₂ + ²Cl + CH₂O, and p,s,o-CH₂ClOOOCl + CH₂O with the energy barriers of 5.6, 11.8, 12.4, 12.4, and 13.5 kcal/mol, respectively. Their mechanisms are that CH₂ClO₂ and CH₂ClO₂ form a tetroxide intermediate first, then the intermediate dissociates to yield the productions or through multi-steps reactions to produce the final products.

Three-dimensional (3D) quantitative structure–activity relationships (QSARs) of 36 apoptosis inducers, substituted 4-aryl/heteroaryl-4H-chromenes with anticancer activity against human breast cancer cell lines T47D, have been studied by using methods of comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA). The established 3D-QSAR models in training set show not only significant statistical quality, but also predictive ability, with high correlation coefficient (R²) values and cross-validation coefficient (q²) values: CoMFA (R², q²: 0.944, 0.747), CoMSIA (R², q²: 0.944, 0.704). Moreover, the predictive abilities of the CoMFA and CoMSIA models were further confirmed by a test set, giving the predictive correlation coefficients ( values) of 0.845 and 0.851, respectively. Based on the CoMFA and CoMSIA contour map analyses, some key factors responsible for anticancer activity of this series of compounds have been found as follows: the steric interaction plays a decisive role in determining the anticancer activities of these compounds; bulky groups as substituent R₁ are not tolerated; in addition to a steric moderation, higher degree of electropositivity and hydrophobicity on the terminal alkyl of substituent R₂ might be favorable to the activity; the substituent R₃ should be hydrophobic; bulky and strong electron withdrawing groups for the substituent R₄ are not advantageous to the activity; simultaneously introducing large electronegative atoms as hydrogen-acceptors to the first atoms of the substituents R₅ and R₆ may increase the activity, but substituents R₅ and R₆ with a linking group –OCH₂O– may decrease the activity. Such results can offer some useful theoretical references for understanding the action mechanism, designing more potent derivatives, and predicting their activities prior to synthesis.

A time-dependent formulation of quantum control is employed to investigate optimally controlled vibrational population transfer in a diatomic quantum system. The problem of finding the optimal laser field needed to achieve a specific quantum transition from an initial state to the desired target goal is formulated using an iterative method and the conjugate gradient method (CGM). The time-dependent Schrödinger equation is solved with interaction of laser radiation with matter included within a dipole approximation in the Hamiltonian. Appropriate boundary conditions are chosen for the evolution problem. The control objective is chosen as the value of transition probability from an initial state to a target state. A comparison is made between the results obtained using the iterative method and the CGM for optimization. Finally, quantum bits are encoded using the vibrational states of the diatomic in the regime of low-vibrational excitation.