Background: Aurora kinases perform important roles in mammals, mainly in cell cycle. Overexpression of these enzymes is related to tumor development and is indicative of worsening of clinical conditions. Aurora kinases are promising targets in the search for new anticancer drugs, in particular, Aurora B. </P><P> Methods: This work was designed to study and understand the interactions between human Aurora B and several indolin-2-one derivatives, structurally similar to sunitinib. MVD software was utilized in docking analyses of indolin-2-one derivatives. Human Aurora B kinase was obtained from the PDB (4AF3) and redocked with hesperadin, which was used as a reference compound. The predicted model of the training group, considering 21 amino acid residues, performed in Chemoface, achieved an R2 of 0.945, suggesting that the binding conformations of the ligands with human Aurora B are reasonable and the data can be used to predict the interaction energy of other Aurora B inhibitors indolin-2-one derivatives. Results: MolDock Score energy for compound 1 showed more stable interaction energy (-225.90 kcal.mol-1) then the other inhibitors studied, while sunitinib was the least stable (-135.63 kcal.mol-1). Compounds 1-45, hesperadin and sunitinib, interacted with Glu171 (–NH from indolinonic moiety), and the majority of them with Ala173 (C=O from indolinonic moiety) via hydrogen bonds, thus these two residues are relevant for potency. Conclusion: Docking studies and biological activity in literature show subunits likely for structural optimizations, leading to four new proposed derivatives (IAF61, IAF63, IAF66, IAF79) as promising compounds for synthesis and biological evaluation against human Aurora B, validating and ratifying the docking studies.

A series of pyridylthiazole derivatives developed by Lawrence et al. as Rho-associated protein kinase inhibitors were subjected to four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis. The models were generated applying genetic algorithm (GA) optimization combined with partial least squares (PLS) regression. The best model presented validation values ofr2=0.773,qCV2=0.672,rpred2=0.503,Δrm2=0.197,rm test2⁡⁡=0.520,rY-rand2=0.19, andRp2=0.590. Furthermore, analyzing the descriptors it was possible to propose new compounds that predicted higher inhibitory concentration values than the most active compound of the series.

In this study, quantitative structure-activity relationship studies which make use of molecular dynamics trajectories were performed on a set of 54 glucokinase protein activators. The conformations obtained by molecular dynamics simulation were superimposed according to the twelve alignments tested in a virtual three-dimensional box comprised of 2 Å cells. The models were generated by the technique that combines genetic algorithms and partial least squares. The best alignment models generated with a determination coefficient (r(2)) between 0.674 and 0.743 and cross-validation (q(2)) between 0.509 and 0.610, indicating good predictive capacity. The 4D-QSAR models developed in this study suggest novel molecular regions to be explored in the search for better glucokinase activators.

Leishmania donovani is a parasite that causes visceral leishmaniasis, a severe form of leishmaniasis that affects vital organs. An important target for the treatment of this disease is the protein -tubulin, which was modeled in this paper and proposed as a target for the treatment of visceral leishmaniasis. Two classes of compounds were studied, dinitroanilines and oxadiazoles. According to the docking results, dinitroanilines interact better with the L loop domain and oxadiazoles interact better with the colchicine domain. Experimental2.1. Homology Modeling. The modeling began with the systematic search in the database Expasy [11] for primary structures of the protein -tubulin in LdTUB using the server Protein Knowledgebase (UniProtKB) [12] as a search tool. Thus, we obtained the primary alpha (Q25262 LEIDO, 451 amino acids) and beta (I3W8N7 LEIDO, 442 amino acids) sequences. The crystal structure of pig tubulin heterodimer (protein data bank code: 1TUB) was chosen as the template for the construction of the three-dimensional LdTUB model, as it showed the highest sequence identity therewith [13].

Chemical weapons are a major worldwide problem, since they are inexpensive, easy to produce on a large scale and difficult to detect and control. Among the chemical warfare agents, we can highlight the organophosphorus compounds (OP), which contain the phosphorus element and that have a large number of applications. They affect the central nervous system and can lead to death, so there are a lot of works in order to design new effective antidotes for the intoxication caused by them. The standard treatment includes the use of an anticholinergic combined to a central nervous system depressor and an oxime. Oximes are compounds that reactivate Acetylcholinesterase (AChE), a regulatory enzyme responsible for the transmission of nerve impulses, which is one of the molecular targets most vulnerable to neurotoxic agents. Increasingly, enzymatic treatment becomes a promising alternative; therefore, other enzymes have been studied for the OP degradation function, such as phosphotriesterase (PTE) from bacteria, human serum paraoxonase 1 ( Hss PON1) and diisopropyl fluorophosphatase (DFPase) that showed significant performances in OP detoxification. The understanding of mechanisms by which enzymes act is of extreme importance for the projection of antidotes for warfare agents, and computational chemistry comes to aid and reduce the time and costs of the process. Molecular Docking, Molecular Dynamics and QM/MM (quantum-mechanics/molecular-mechanics) are techniques used to investigate the molecular interactions between ligands and proteins.