ABSTRACT
In this work, we performed a study to assess the interactions between the ricin toxin A (RTA) subunit of ricin and some of its inhibitors using modern semiempirical quantum chemistry and ONIOM quantum mechanics/molecular mechanics (QM/MM) methods. Two approaches were followed (calculation of binding enthalpies, ΔH bind, and reactivity quantum chemical descriptors) and compared with the respective half-maximal inhibitory concentration (IC50) experimental data, to gain insight into RTA inhibitors and verify which quantum chemical method would better describe RTA-ligand interactions. The geometries for all RTA-ligand complexes were obtained after running classical molecular dynamics simulations in aqueous media. We found that single-point energy calculations of ΔH bind with the PM6-DH+, PM6-D3H4, and PM7 semiempirical methods and ONIOM QM/MM presented a good correlation with the IC50 data. We also observed, however, that the correlation decreased significantly when we calculated ΔH bind after full-atom geometry optimization with all semiempirical methods. Based on the results from reactivity descriptors calculations for the cases studied, we noted that both types of interactions, molecular overlap and electrostatic interactions, play significant roles in the overall affinity of these ligands for the RTA binding pocket.
ABSTRACT
Alloy clusters of NaxLiy (4 ≤ x + y ≤ 10) are studied by exploring the potential energy surface in the ab initio MP2 level with the support of a quantum genetic algorithm (QGA). In some cases, the structures have been also refined with DFT and coupled-cluster methods. The general trends of sodium-lithium structures are in line with previous studies. The ionization potentials and polarizabilities to all structures were calculated with MP2 method and the average error between these two properties compared with experimental data was 6% and 13%, respectively. The topological analysis based on quantum theory of atoms in molecules (QTAIM) showed that by increasing the cluster size of the diatomic system there was a decrease of atomic interaction energies. The degree of degeneracy from D3BIA aromaticity index and the analysis of the atomic charges showed the influence (by charge transfer) of the chemical element in lower quantity in the cluster with respect to the other atoms. Our achievements of comparing our theoretical results with available experimental data have demonstrated that our approach can also predict satisfactorily quantum atomic and alloy clusters properties, at least, for low nuclearities.
