Molecular Docking of Azadirachtin in Nuclear Ecdysone Receptor

Background: The azadirachtin is a triterpenoid associated with growth inhibition in several kinds of insects which cause epidemic diseases like Dengue, Chikungunya and Malaria. Azadirachtin acts by inhibiting the Ecdysone Receptor (EcR), which is responsible from larvae phase in insects. However, the interaction between the azadirachtin molecule and the Ecdysone Receptor is unknown. In this work, we used the program Dock Thor to generate several azadirachtin conformations inside the EcR binding site. The ten most stable conformations were optimized with the ONIOM approach present in the Gaussian 09 program. The interaction energy was calculated between the azadirachtin molecule and EcR receptor. Theoretical calculation shows that the azadirachtin molecule interacts with the same amino acids present in the ecdysone EcR interaction. These results will be useful to design new EcR inhibitors, which can be used in the control of some diseases based on insect proliferations. Objective: To understand the interaction between the natural insecticide azadirachtin and the Ecdysone Receptor. Methods: A combination of Dock Thor program with QM-MM calculation was used in order to obtain the most favorable molecular structures. Results: The hydrogens bond obtained by Dock Thor Program combined with QM-MM calculation suggest the azadirachtin interact with EcR in the same way that ecdysone molecule. Conclusion: The interaction mode that the molecule azadirachtin inhibits EcR in order to avoid insect proliferation was described.

Temperature dependence of Uiso constraints in riding hydrogen treatments

"Anisotropic parametrisation of the thermal displacements of hydrogen atoms in single-crystal X-ray structure refinement is not possible with independent atom model (IAM) scattering factors. This is due to the weak scattering contribution of hydrogen atoms. Only when aspherical scattering factors are used can carefully measured Bragg data provide such information. For conventional structure determinations parameters of ""riding"" hydrogen atoms are frequently constrained to values of their ""parent"" heavy atom. Usually values of 1.2 and 1.5 times X-U_eq are assigned to H-U_iso in these cases. Such constraints yield reasonable structural models for room-temperature data. However, todays small molecule X-Ray diffraction experiments are usually carried out at significantly lower temperatures. To further study the temperature dependence of ADPs we have evaluated several data sets of N-Acetyl-L-4-Hydroxyproline Monohydrate at temperatures ranging from 9 K to 250 K. Methods compared were HAR [1], Invariom refinement [2], time-of-flight Neutron diffraction and the TLS+ONIOM approach [3]. In the TLS+ONIOM approach non-hydrogen ADPs from Invariom refinement provided ADPs for the TLS-fit. Hydrogen atoms in all methods were grouped and analyzed according to their Invariom name. We reach a good agreement of the temperature dependence of H-U_iso/X-U_eq. At very low temperatures the ratio H-U_iso/X-U_eq can be as high as 4, e.g. for Hydrogen attached to a sp3 carbon atom with three non-Hydrogen atom neighbors. Since all methods consistently show that the H-U_iso/X-U_eq ratio is temperature dependent, this effect should be taken into account in conventional structure determinations."