Journal of Theoretical and Computational Chemistry

Cardiac Troponin T (cTnT) is a central modulator of thin filament regulation of myofilament activation. The lack of structural data for the TNT1 tail domain, a proposed α-helical region, makes the functional implications of the FHC mutations difficult to determine. Studies have suggested that flexibility of TNT1 is important in normal protein–protein interactions within the thin filament. Our groups have previously shown through molecular dynamics (MD) simulations that some FHC mutations, Arg92Leu (R92L) and Arg92Trp (R92W), result in increased flexibility at a critical hinge region 18 Angstroms distant from the mutation. To explain this distant effect and its implications for FHC mutations, we characterized the dynamics of wild type and mutational segments of cTnT using MD. Our data shows an opening of the helix between residues 105–110 in mutants. Consequently, the dihedral angles of these residues correspond to non-α-helical regions on Ramachandran plots. We hypothesize the removal of a charged residue decreases electrostatic repulsion between the point mutation and the surrounding residues resulting in local helical compaction. Constrained ends of the helix and localized compaction result in expansion within the nearest non-charged helical turn from the mutation site, residues 105–109.

The torsional potential function for methyl rotation in dimethyl ether (DME) and dimethyl sulfide (DMS) has been determined by utilizing ab initio (Hartree–Fock and MP2) and density functional theory (B3LYP, B3P86, and B3PW91) methods along with several basis sets. Natural bond orbital (NBO) analysis was also applied to investigate the origin of the rotational barrier.

In the present study, the relationship between the topochemical indices and log P values of 1,3-disubstituted propan-2-one analogs has been investigated. Three topochemical indices, Wiener's topochemical index — a distance-based topochemical descriptor, molecular connectivity topochemical index — an adjacency-based topochemical descriptor, and eccentric connectivity topochemical index — an adjacency-cum-distance-based topochemical descriptor, were used for the present investigation. The values of the Wiener's topochemical index, molecular connectivity topochemical index, and eccentric connectivity topochemical index were computed for each of the 45 analogs constituting the data set using an in-house computer program. The predicted log P values using leave-one-out (LOO) procedure exhibited a q² of 0.72, 0.70, and 0.71 with reported log P values for Wiener's topochemical index, molecular connectivity topochemical index, and eccentric connectivity topochemical index, respectively. Separate models were developed using training set and log P of each analog in the independent test set was predicted using these models. The correlation of predicted log P values with the reported values, for independent test set, were in good agreement with those predicted using LOO procedure.

The N–O bond dissociation energies (BDEs) and the heats of formation (HOFs) of alkyl nitrate and nitrite compounds in gas phase at 298.15 K were theoretically calculated. Density functional theory (B3LYP and PBE1PBE) with 6-311+g** and 6-311g** basis sets was employed. It is found that PBE1PBE functional has an average increased BDE of 4.03 kcal/mol from B3LYP functional. What is more, we find the reverse trend in ab initio approach, which is slightly smaller than PBE1PBE. The B3LYP functional is found to be sufficiently reliable to compute the BDEs of alkyl nitrate compounds without the presence of diffusion functions. The BDEs of alkyl nitrite compounds appear to be a constant. The functionals (B3LYP and PBE1PBE) with 6-311g** and 6-311+g** basis sets and CBS-4M ab initio method can all yield good results with respect to the experimental HOFs with the deviation less than 2.0 kcal/mol. As the number of methylene group increases, the HOFs of alkyl nitrate and nitrite compounds increase. In addition, the conclusion of Ventural et al. (J Phys Chem A105:9912, 2001 and Phys Lett245:488, 1995) is confirmed again by our computational results.

In this paper, molecular structures and vibrational frequencies of cycloketone, cyclopropanone, cyclobutanone, cyclopentanone, and cyclohexanone have been investigated by density functional theory (DFT) and the second order Møller and Plesset (MP2) levels of theory, using 6-311G, 6-311G**, 6-311++G, and 6-311++G** basis sets.

The calculations predict a planar structure for cyclopropanone. The cyclobutanone ring is puckered and according to the calculations at B3LYP/6-311++G** and MP2/6-311++G** levels of theory, it deviates from planarity by 5.0° and 15.7°, respectively. The calculated barrier height between puckered and planar conformer, at MP2/6-311G** level of theory, is 196.7 cm^-1. The puckering frequency at B3LYP/6-311G** and MP2/6-311G** levels are 47.5 cm^-1 and 121.2 cm^-1. Cyclopentanone has twisted conformations (C₂ symmetry) in which carbons C1 and C2 are out-of-plane with a torsional angle of 11.5° (MP2/6-311G**) and the molecule goes from one conformation to the other via an envelope transition conformation (C_s symmetry). or planar hilltop conformation (C_2v symmetry). The most stable conformation of the cyclohexanone is C_s chair, which has no ring strain, is used as land mark.

In this paper, a method for calculating all the Hückel molecular orbitals (MO) of large (16.000 atoms) carbon zigzag nanotubes is presented. These MO have been obtained by combining the singular value decomposition (SVD), the Sylvester–Hadamard transform, and the theory of Hamiltonian–Symplectic matrices. Numerical diagonalization of hermitian matrices is reviewed and improved. A new, more advantageous, (tri-diagonal) algorithm is proposed and analyzed. The reactivity of the atoms is described by calculating their free valence indices.

Structural and electronic properties of Sr(N₃)₂ under pressure up to 120 GPa are studied by means of SIESTA calculation. The pressure–angle as well as the cell parameters relation respect to pressure is employed to study the structural changes under pressure. The obtained N–N bond length at zero pressure is in agreement with the other works. The energy band gap takes on the trend of decreasing below 20 GPa and this trend could result in the reduction of the stability for Sr(N₃)₂ crystal, but at 30 GPa it increases suddenly. And polymorphic transformation is observed. The ionic configuration for Sr(N₃)₂ in the fundamental state is estimated to be Sr^+1.200N^-0.200. The charge density of N atom is more sensitive to pressure variation than that of Sr atom.

Support vector machine (SVM) is used to predict the enthalpies of formation at 298 K for 261 molecules based on B3LYP/6-311g (3df,2p) results. With data randomly separated into two parts: 195 for training set and 66 for test set, the resulting mean absolute deviation (MAD) and maximum deviation (MD) for training set are 1.51 kcal/mol and 9.23 kcal/mol (correlation coefficient R = 0.9995), and for test set they become to 1.78 kcal/mol and 7.31 kcal/mol (R = 0.9990). The result is improved according to G2 method.

Triphenyldichlorophosphorane (Ph₃PCl₂) in solution was studied with cluster model of discrete water molecules and the Onsager reaction field model. The geometry of Ph₃PCl₂–H₂O cluster is optimized with DFT-PW91 and DZVP basis sets. A weak hydrogen bond is formed between Cl and H atom of the water molecule. The geometry data of Ph₃PCl₂ molecule is altered due to the presence of water molecule. The bond length of P–Cl₂ increases from 2.501 Å to 2.832 Å, and the P–Cl₁ bond length decreases from 2.113 Å to 2.064 Å. Three C–P bonds have slightly changed. The geometrical parameters of the three benzene rings do not change much upon clustering. To compare with solution structure, gas structure of Ph₃PCl₂ also was investigated. Four stationary structures were found. The trigonal bipyramidal structure C is a penta-coordinated structure and the most stable one. This is in agreement with the previous research. The trigonal bipyramidal structure C and the ionic structure A has no imaginary frequency. The structure B and structure D have an imaginary frequency of -41.9 cm^-1 and -7.4 cm^-1, respectively.

The adsorption of CN on Cu(111) has been investigated using density functional theory calculations based on plane-wave expansion and pseudo-potential treatment. Calculations within the generalized gradient approximation predicted a preference for CN in the fcc C-down site. No stationary points corresponding to pure parallel mode were found. But the tilted mode was found to be achievable. The calculated vibrational frequencies of CN were used to correctly discriminate between the adsorption sites.

Theoretical investigations are preformed on the model reaction of PH₃CH + H₂CO to unravel reactivity of PH₃CH, so-called Ylide-like radical, at G3MP2 and CCSD(T)/aug-cc-pVDZ//MP2/6-311++G(d,p) level. The results indicate that P-Ylidic radical behaves differently from the P-Ylide or usual unsaturated radical toward formaldehyde. For the entrance channels, [2+2] cycloaddition to form oxaphosphetane radical INT1 is more favorable, which is an analogical process to Witting reaction of P-Ylide. So PH₃CH shows P-Ylide character in entrance channel, which has found the support from the dual one-center frontier–orbital interaction based on Fukui's frontier–orbital theory. However, due to the radical character of INT1, it can competitively give P₂PH₃CHCHO + H and INT2, but not Witting-type products of alkene and phosphine oxide. At last, INT2 almost can barrierlessly fragmentate to Corey-type products of ethene oxide radical and phosphine. The present study shows that PH₃CH, Ylide-like radical, has duplicate reactivity of both P-Ylide and radical, and title reaction presents a completely new reaction mechanism, compared with previous well-known H-abstract or addition–elimination mechanism for radical-H₂CO reactions.

With the aid of the automatic molecular docking, the affinity of CYP2C9 and CYP2D6 for imrecoxib was studied by InsightII/Affinity program. The results indicate that CYP2C9–imrecoxib complex has higher stability and stronger affinity because CYP2C9 has more favorable interaction energy (-62.72 kcal/mol) and higher Ludi score (610) with imrecoxib than CYP2D6 (-50.22 kcal/mol and 551) and this is consistent with the results of the kinetic experiments by Li et al. By analyzing the theoretical results combined with the experimental ones, we suggest that the affinity difference is caused by the difference of the structure between CYP2C9 and CYP2D6, and the most important residues for enzyme–substrate complexes, such as Phe476, Asn204, Phe100, Leu366 and Arg108 of CYP2C9 and Phe120, Glu216, and Phe483 of CYP2D6 were also identified.

The transition states for the H₂NO decomposition and rearrangements mechanisms have been explored by the CBS-Q method or by density functional theory. Six transition states were located on the potential energy surface, which were explored with the Quadratic Complete Basis Set (CBS-Q) and Becke's one-parameter density functional hybrid methods. Interesting deviations between the CBS-Q results and the B1LYP density functional theory lead us to believe that further study into this system is necessary. In the efforts to further assess the stabilities of the transition states, bond order calculations were performed to measure the strength of the bonds in the transition state.

In this paper, we present progress in the application of the explicitly time-dependent multi-configuration time-dependent Hartree–Fock (MCTDHF) method. The spin–orbitals and equations of motion are expressed in the basis of Gaussian Type Orbitals. MCTDHF is then applied to the calculation of the electronic ground state of various small molecules by imaginary time propagation. We were able to take between four and 12 active electrons into account. We discuss the suitability of a core guess as initial wave function, the possibility to obtain excited states, as well as the consequences of a neglect of core excitations.

In the course of an extensive investigation aimed at understanding the detailed mechanism of a prototypical polyatomic reaction, several remarkable observations were uncovered. To interpret these findings, we surmise the existence of a reactive resonance in this polyatomic reaction. The system of concern is X + H₂O → XH + OH (X = Cl, F, H), and it belongs to a type of asymmetrical H exchanging reaction. Because the concerned electronic number is quite small, it is usually regarded as a template constructed the model of theory or experiment. In this paper, compared with the symmetrical systems, we constructed the partial potential surfaces of asymmetrical systems in order to research their resonance states. All results are in good agreement with previous theoretical and experimental works.

Time-dependent density functional theory (TD-DFT) formalism is employed to calculate the electronic spectra of A₃B₃ II–VI semiconductor clusters based on the geometrical structures optimized at DFT-B3LYP level. Moreover, their second-order nonlinear optical (NLO) properties are performed by TD-B3LYP combined with sum-over-states (SOS) formula. The calculation results indicate that it is necessary to consider the effective core potential and electron correlation effects when the basis sets are chosen for the heavy atoms. In addition, the results show that the transition energies and HOMO–LUMO gaps of the A₃B₃ II–VI semiconductor clusters decrease, while the second-order nonlinear optical responses increase with the increasing of VI-group ionic radius. As a result, the SOS formula is valuable to calculate the β_μ in the summation of 120 states. Meanwhile, charge transfers from the π bonding to π anti-bonding orbitals between II and VI group atoms significantly contribute to the second-order NLO properties.

The structure, stability, and properties of the hydrated clusters of calcium hydroxide, Ca(OH)₂(H₂O)_n, n = 1–6, were investigated using density functional and ab initio quantum chemical methods. The results show that six water molecules are needed to result in the complete dissociation of Ca(OH)₂. The stable and ionic conformer of Ca(OH)₂(H₂O)₆ has C₃ symmetry. Its surprising stability and high IR activity render hydrated clusters of Ca(OH)₂ potentially significant in the nucleation of noctilucent clouds in the mesosphere. Trends in the interaction energies (ΔE_e) of the complexes show that water molecules in the first shell of Ca²⁺ are highly stable, further alluding to the role of hydrated Ca(OH)₂ in aerosol formation.

In this paper, we explore the possibility of a small water cluster composed of three water molecules in forming stable dipole-bound anions with molecular surfaces. Our recent results show that charge pockets on surfaces can form by which OH groups situated on one side of the surface (that create hydrogen bonded networks) coupled to the hydrogen atoms on the opposite side of a surface can form positive charge pockets that attracts negative charge. These charge pockets from the molecular surfaces can align with the dipole moment generated by the small (H₂O)₃ cluster to increase the stability of the resulting dipole-bound anion.

Molecular mechanics (MM) method followed by molecular dynamics (MD) simulation was carried out to investigate the stability of an aggregate formed by self-assembling of peptide amphiphile (PA) molecules. The MM + MD simulation confirms that the cylindrical shaped aggregate is very stable. The analysis showed that the remarkable stability of the aggregate was partly due to various intermolecular hydrogen-bond interactions between polar groups of PA molecules. The hydrophobic alkyl tails of PA molecules are packed loosely inside the interior of the aggregates. The packing of alkyl tails contribute further stability of the PA aggregate. Our simulations reproduce qualitatively experimental observations and support the fact that PA molecules are self-assembled within closed intermolecular distance to favor the forming of disulfide bonds.

Chloroethylnitrosoureas (CENUs) are clinically useful anticancer agents. Their cytotoxicity is associated with the generation of DNA interstrand crosslinks. QM/MM computations are carried out to investigate DNA crosslinks by CENUs with ONIOM hybrid method. The crosslinked DNA are subdivided into three layers, each of which are described at B3LYP/6-311+G(d,p), AM1, and UFF level of theory, respectively. The result shows that the deformation of DNA with dG(N¹)–dC(N³) crosslink is much less than the other crosslinks, which indicate that the most favorable crosslink is between the N¹ atom of guanine and the N³ atom of the complementary cytosine.

Using complete orthonormal sets of Ψ^α-exponential type orbitals (Ψ^α-ETO, α = 1, 0, -1, -2,…), the three-center overlap integrals over noninteger n STO (NISTO) appearing in the evaluation of multicenter–multielectron integrals of central and noncentral interaction potentials are calculated. The final results are expressed in terms of one- or two-center overlap integrals between NISTO and integer n STO (ISTO). The formulas obtained are valid for arbitrary noninteger principal quantum numbers, screening parameters, and location of NSTO.