Bioactive compounds from Morchella esculenta as potential inhibitors of RNA-binding protein La in ovarian cancer: a molecular modeling and quantum mechanics approach.

La protein is significantly expressed in various malignant tumors, including ovarian cancer (OC), which is related to the poor response to platinum-based chemotherapy. Thus, inhibiting La protein could control the expression of the potential downstream genes involved in promoting proliferation and chemotherapy resistance to OC, which could serve as a therapeutic intervention. Through a molecular docking approach, 12 compounds from Morchella esculenta were screened against the crystal structure of La protein and four hit compounds were identified, including beta-carotene, p-hydroxybenzoic acid, gamma-tocopherol, and alpha-tocopherol, with a binding affinity of - 10.7, - 8.1, - 7.9, and - 7.6 kcal/mol, respectively, higher than pyridine-2-carboxylate (control), with a binding affinity of - 5.2 kcal/mol. To explore the interaction of the hit compounds with the target receptor, they were selected for a molecular dynamic simulation and post-simulation analysis for 100 ns. The result showed promising reliability of the ligands due to a stable interaction with the La protein crystal structure. Furthermore, the drug-likeness and physicochemical chemical properties of the compounds were investigated using ADMET study and density functional theory analysis, respectively, and the result shows that the hit compounds could serve as a promising starting for the development of novel LA protein inhibitors for OC therapeutics. Finally, this study compared HOMO and LUMO values from global hybrids with long-range corrected DFAs, and the result from the two followed the same qualitative pattern while calculating HOMO values; however, MO62X/cc-pVTZ could better predict LUMO values when considering a global hybrid.

Correlation consistent basis sets designed for density functional theory: Third-row atoms (Ga-Br).

The correlation consistent basis sets (cc-pVnZ with n = D, T, Q, 5) for the Ga-Br elements have been redesigned, tuning the sets for use for density functional approximations. Steps to redesign these basis sets for an improved correlation energy recovery and efficiency include truncation of higher angular momentum functions, recontraction of basis set coefficients, and reoptimization of basis set exponents. These redesigned basis sets are compared with conventional cc-pVnZ basis sets and other basis sets, which are, in principle, designed to achieve systematic improvement with respect to increasing basis set size. The convergence of atomic energies, bond lengths, bond dissociation energies, and enthalpies of formation to the Kohn-Sham limit is improved relative to other basis sets where convergence to the Kohn-Sham limit is typically not observed.

Comparative Study of Nonhybrid Density Functional Approximations for the Prediction of 3d Transition Metal Thermochemistry.

The utility of several nonhybrid density functional approximations (DFAs) is considered for the prediction of gas phase enthalpies of formation for a large set of 3d transition metal-containing molecules. Nonhybrid DFAs can model thermochemical values for 3d transition metal-containing molecules with accuracy comparable to that of hybrid functionals. The GAM-generalized gradient approximation (GGA); the TPSS, M06-L, and MN15-L meta-GGAs; and the Rung 3.5 PBE+ΠLDA(s) DFAs all give root-mean-square deviations below that of the widely used B3LYP hybrid. Modern nonhybrid DFAs continue to show utility for transition metal thermochemistry.

Tunable fictitious substituent effects on the π-π interactions of substituted sandwich benzene dimers.

Substituent effects on the π-π interactions of aromatic rings are a topic of much recent debate. Real substituents give a complicated combination of inductive, resonant, dispersion, and other effects. To help partition these effects, we present calculations on fictitious "pure" σ donor/acceptor substituents, hydrogen atoms with nuclear charges other than 1. "Pure" σ donors with nuclear charge <1 weaken π-π stacking in the sandwich benzene dimer. This result is consistent with the electrostatic model of Hunter and Sanders, and different from real substituents. Calculated inductive effects are largely additive and transferable, consistent with a local direct interaction model. A second series of fictitious substituents, neutral hydrogen atoms with an artificially broadened nuclear charge distribution, give similar trends though with reduced additivity. These results provide an alternative perspective on substituent effects in noncovalent interactions.

Toward accurate theoretical thermochemistry of first row transition metal complexes.

The recently developed correlation consistent Composite Approach for transition metals (ccCA-TM) was utilized to compute the thermochemical properties for a collection of 225 inorganic molecules containing first row (3d) transition metals, ranging from the monohydrides to larger organometallics such as Sc(C(5)H(5))(3) and clusters such as (CrO(3))(3). Ostentatiously large deviations of ccCA-TM predictions stem mainly from aging and unreliable experimental data. For a subset of 70 molecules with reported experimental uncertainties less than or equal to 2.0 kcal mol(-1), regardless of the presence of moderate multireference character in some molecules, ccCA-TM achieves transition metal chemical accuracy of ±3.0 kcal mol(-1) as defined in our earlier work [J. Phys. Chem. A2007, 111, 11269-11277] by giving a mean absolute deviation of 2.90 kcal mol(-1) and a root-mean-square deviation of 3.91 kcal mol(-1). As subsets are constructed with decreasing upper limits of reported experimental uncertainties (5.0, 4.0, 3.0, 2.0, and 1.0 kcal mol(-1)), the ccCA-TM mean absolute deviations were observed to monotonically drop off from 4.35 to 2.37 kcal mol(-1). In contrast, such a trend is missing for DFT methods as exemplified by B3LYP and M06 with mean absolute deviations in the range 12.9-14.1 and 10.5-11.0 kcal mol(-1), respectively. Salient multireference character, as demonstrated by the T(1)/D(1) diagnostics and the weights (C(0)(2)) of leading electron configuration in the complete active self-consistent field wave function, was found in a significant amount of molecules, which can still be accurately described by the single reference ccCA-TM. The ccCA-TM algorithm has been demonstrated as an accurate, robust, and widely applicable model chemistry for 3d transition metal-containing species with versatile bonding features.

Modeling the photophysics of Zn and Cd monomers, metallophilic dimers, and covalent excimers.

Density functional (Xα, BLYP, BPW91, B3LYP, and B3PW91), MP2, and coupled cluster with singles, doubles, and quasiperturbative triple excitations (CCSD(T)) methods in combination with LANL2DZ, cc-pVxZ, cc-pVxZ-PP, or cc-pVxZ-DK (where x = D (double), T (triple) Q (quadruple), and 5 (quintuple)) basis sets have been employed in computations of excited states of zinc and cadmium dimers and monomers. The spectroscopic constants r(e), D(e), T(e), ω(e), ω(e)x(e), and B(e) are compared among group 12 dimers in their ground and low-lying phosphorescent excited states. The weak metallophilic bonding in the ground state requires MP2 or CCSD(T) description, whereas the excimeric bonding is well described by CCSD(T), BLYP, B3LYP, BPW91, and B3PW91. Consistent with our previous work on Hg(n) species, absorption and phosphorescence transition energies that agree well with experimental results can be obtained with CCSD(T) and B3PW91 methods in combination with the correlation consistent basis sets of triple-ζ or higher level. This is the case for monomers and *Cd(2) and *Zn(2) lowest triplet excimers (in either the (3)Σ(u)(+) or (3)Π(g) state). The CCSD(T)/aug-cc-pV5Z-PP combination results in values that are only 150 and 240 cm(-1) (<1% errors) removed from the experimental values for the (1)S → (3)D atomic transitions for Zn and Cd, respectively. Such spectroscopic constants provide the most accurate theoretical values known to date for bonding and photophysical parameters characteristic of Zn(n) and Cd(n) species.