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The blair witch project 23/1/2023 ![]() ![]() In addition, it has been observed that the hydrophobic complementarity of the domain is exerted by the base interactions of the GAGA loop structure. The individual components (by amino acid residue) of the binding free energy of the RTA–RNA complex revealed highly relevant electrostatic interactions arising from the charge–charge complementarity of the interfacial arginines with the RNA phosphate backbone. In addition, it was observed that the terms of free energies presented unfavorable electrostatic contributions that were balanced by the favorable nonspecific hydrophobic effect, with free energies similar to those of protein–protein complexes. ![]() The authors found that the absolute free energies of formation obtained for the RTA–RNA complex, as well as for several protein mutants, presented good agreement with the experimental data. In another report, Olson and Cuff (54) expanded the previous study (53) by analyzing the free-energy determinants for the formation of RTA complexes with the rRNA substrate and several small ligands. 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. We also observed, however, that the correlation decreased significantly when we calculated Δ H bind after full-atom geometry optimization with all semiempirical methods. We found that single-point energy calculations of Δ H bind with the PM6-DH+, PM6-D3H4, and PM7 semiempirical methods and ONIOM QM/MM presented a good correlation with the IC 50 data. The geometries for all RTA–ligand complexes were obtained after running classical molecular dynamics simulations in aqueous media. ![]() Two approaches were followed (calculation of binding enthalpies, Δ H bind, and reactivity quantum chemical descriptors) and compared with the respective half-maximal inhibitory concentration (IC 50) experimental data, to gain insight into RTA inhibitors and verify which quantum chemical method would better describe RTA–ligand interactions. 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. ![]()
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