Tikhonov regularization is an usual method to solve an ill-posed problem, recommended when the input data are contaminated with noise. However, in some cases, the use of this technique is not sufficient to provide good solutions. In this work, an improvement of the Tikhonov regularization method was proposed and tested in the inverse black body radiation problem. The method proposed consisted in including the norm of the fractional-order derivative of the solution in the original functional proposed by Tikhonov. In the present framework, the regularized solution depends on the regularization parameter, λ, and on the fractional derivative order, α. For α assuming real value between 0 and 2, the solution obtained is more precise than those from the usual Tikhonov regularization method.

The absence of adequate force field (FF) parameters to describe certain metallic complexes makes new and deeper analyses impossible. In this context, after a group of researchers developed and validated an AMBER FF for a platinum complex (PC) conjugated with AHBT, new possibilities emerged. Thus, in this work, we propose an improved path to obtain NMR spectroscopic parameters, starting from a specific FF for PC, allowing to obtain more reliable information and a longer simulation time. Initially, a docking study was carried out between a PC and PI3K enzyme, aiming to find the most favorable orientation and, from this pose, to carry out a simulation of classical molecular dynamics (MD) with an explicit solvent and simulation time of 50 ns. To explore a new PC environment, a second MD simulation was performed only between the complex and water molecules, under the same conditions as the first MD. After the results of the two MDs, we proposed strategies to select the best amino acid residues (first MD) and water molecules (second MD) through the analyses of hydrogen bonds and minimum distance distribution functions (MDDFs), respectively. In addition, we also selected the best frames from the two MDs through the OWSCA algorithm. From these resources, it was possible to reduce the amount and computational cost of subsequent quantum calculations. Thus, we performed NMR calculations in two chemical environments, enzymatic and aqueous, with theory level GIAO–PBEPBE/NMR-DKH. So, from a strategic path, we were able to obtain more reliable chemical shifts and, therefore, propose safer spectroscopic probes, showing a large difference between the values of chemical shifts in the enzymatic and aqueous environments.

Nerve agents are organophosphates (OPs) that act as potent inhibitors of acetylcholinesterase (AChE), the enzyme responsible for the hydrolysis of acetylcholine. After inhibition, a dealkylation reaction of the phosphorylated serine, known as the aging of AChE, can occur. When aged, reactivators of OP-inhibited AChE are no longer effective. Therefore, the realkylation of aged AChE may offer a pathway to reverse AChE aging. In this study, molecular modeling was conducted to propose new ligands as realkylators of aged AChE. We applied a methodology involving docking and quantum mechanics/molecular mechanics (QM/MM) calculations to evaluate the resurrection kinetic constants and ligand interactions with OP-aged AChE, comparing them to data found in the literature. The results obtained confirm that this method is suitable for predicting kinetic and thermodynamic parameters of ligands, which can be useful in the design and selection of new and more effective ligands for AChE realkylation.