Freely available conformer generation methods: how good are they?

Conformer generation has important implications in cheminformatics, particularly in computational drug discovery where the quality of conformer generation software may affect the outcome of a virtual screening exercise. We examine the performance of four freely available small molecule conformer generation tools (Balloon, Confab, Frog2, and RDKit) alongside a commercial tool (MOE). The aim of this study is 3-fold: (i) to identify which tools most accurately reproduce experimentally determined structures; (ii) to examine the diversity of the generated conformational set; and (iii) to benchmark the computational time expended. These aspects were tested using a set of 708 drug-like molecules assembled from the OMEGA validation set and the Astex Diverse Set. These molecules have varying physicochemical properties and at least one known X-ray crystal structure. We found that RDKit and Confab are statistically better than other methods at generating low rmsd conformers to the known structure. RDKit is particularly suited for less flexible molecules while Confab, with its systematic approach, is able to generate conformers which are geometrically closer to the experimentally determined structure for molecules with a large number of rotatable bonds (≥10). In our tests RDKit also resulted as the second fastest method after Frog2. In order to enhance the performance of RDKit, we developed a postprocessing algorithm to build a diverse and representative set of conformers which also contains a close conformer to the known structure. Our analysis indicates that, with postprocessing, RDKit is a valid free alternative to commercial, proprietary software.     

Gauged galileons from branes

We show how the coupling of SO(N)$\mathit{SO}(N)$ gauge fields to galileons arises from a probe brane construction. The galileons arise from the brane bending modes of a brane probing a co-dimension N bulk, and the gauge fields arise by turning on certain off-diagonal components in the zero mode of the bulk metric. By construction, the equations of motion for both the galileons and gauge fields remain second order. Covariant gauged galileons are derived as well.     

The densities of mixed glass former 0.35 Na2O + 0.65 [xB2O3 + (1 − x)P2O5] glasses related to the atomic fractions and volumes of short range structures

The mixed glass former effect (MGFE) is defined as a non-linear and non-additive change in the ionic conductivity with changing glass former fraction at constant modifier composition between two binary glass forming compositions. In this study, mixed glass former (MGF) sodium borophosphate glasses, 0.35 Na₂O + 0.65 [xB₂O₃ + (1 ? x)P₂O₅], 0 ≤ x ≤ 1, which have been shown to have a strong positive MGFE, have been prepared and their physical properties, density and molar volume, have been examined as predictors of structural change. The density exhibits a strong positive non-linear and non-additive change in the density with x and a corresponding negative non-linear and non-additive change in the molar volume. In order to understand the structural origins of these changes, a model of the molar volume was created and best-fit to the experimentally determined molar volumes in order to determine the volumes of the short range order (SRO) structural units in these glasses, how these volume change from the molar volumes of the binary glasses, and how these volumes change across the range of x in the ternary glasses. The best-fit model was defined as the model that required the smallest changes in the volumes of the ternary phosphate and borate SRO structural groups from their values determined by the densities of the binary sodium phosphate and sodium borate glasses. In this best-fit molar volume model, it was found that the volumes of the various phosphate and borate SRO structural groups decreased by values ranging from a minimum value of ~ 1% for x = 0.1 and 0.9 to a maximum value of ~ 6% for the phosphate and ~ 9% for the borate SRO groups at the minimum in molar volume at x = 0.4. The free volume was found to have a negative deviation from linear which is unexpected given the positive deviation in ionic conductivity.     

The glass transition temperature of mixed glass former 0.35Na2O + 0.65[xB2O3 + (1 − x)P2O5] glasses

The mixed glass former effect (MGFE) is defined as the non-linear and non-additive change in the ionic conductivity with changing glass former fraction at constant modifier composition between two binary glass former compositions. In this study, sodium borophosphate glasses, 0.35Na₂O + 0.65[xB₂O₃ + (1 ? x)P₂O₅] with 0 ≤ x ≤ 1, have been prepared and their glass transition temperatures (T_g) have been examined as an alternative indicator of the MGFE and as an indicator of changes in the short range order (SRO) structural network units that could cause or contribute to the MGFE. The changes in T_g show a positive non-additive and non-linear trend over the changing glass former fraction, x. The increase in T_g is related to the increasing number of bridging oxygens (BO) in the glass samples, which is caused by the increase in the number of tetrahedral boron, B⁴, units in the SRO structure.     

Quadrupole-bound anions: efficacy of positive versus negative quadrupole moments

A pseudopotential method is utilized to study the critical stability of model anions formed by long-range quadrupolar molecular potentials. Results indicate that critical quadrupole moments of simple point-charge triads do not serve well as predictors of real quadrupole-bound anions of systems with negative moments.     

Isotopic oxygen exchange rates between [V18O42]12− and water

Summary From kinetic studies of¹⁸O-exchange between aqueous solutions of K₁₂V₁₈O₄₂ · 16H₂O and water it is concluded that [V₁₈O₄₂]^12– exists as a discrete ion in this medium. The rate of exchange is relatively slow (t_1/2 ca. 6×10⁴s at 0°C) and obeys the McKay equation within the precision obtainable. The sensitivity of the ion to its environment in the solid state, leading to induced exchange, prevented a decision as to whether all oxygens are kinetically equivalent. It is clear, however, that the ions remains intact for long periods in solution in the absence of air.     

The convexity lattice of a poset

The authors investigate the lattice Co(P) of convex subsets of a general partially ordered set P. In particular, they determine the conditions under which Co(P) and Co(Q) are isomorphic; and give necessary and sufficient conditions on a lattice L so that L is isomorphic to Co(P) for some P.     

Signature-dependent ml and e2 transition probabilities in 155ho and 157ho

¹⁵⁵Ho and ¹⁵⁷Ho have been populated in the reactions ¹⁴¹Pr(¹⁸O,4n) and ¹⁴⁶Nd(¹⁵N, 4n) at 85 and 74 MeV, respectively. In both nuclei bands built on the $\text{7}\text{2}$?[523] configuration were established to spin values considerably above the first backbend. A signature dependence in the excitation energies as well as in the ratio of M1 to E2 transition rates is observed below, but not above, the backbend in both nuclei. In ¹⁵⁷Ho lifetimes were measured with the recoil-distance method. The ΔI = 2; E2 transition probabilities obtained show very little variation with either signature or spin and no irregularity at the backbend. The signature dependence and strong rise in the ratio B(M1)/B(E2) observed at the backbend in ¹⁵⁷Ho therefore must be caused by the B(M1) values. A signature dependence in the B(E2, I → I ?1)/B(E2, I → I ?2) ratios also found in ¹⁵⁷Ho below the backbend is mainly the result of signature dependence in the ΔI = 1 ; E2 transition rates. Qualitatively, most of the features observed can be explained by nonaxial deformations, which change from large negative to slightly positive values of γ at the backbend.