Molecular Dynamics (MD) simulations is a computational method that employs Newton's laws to evaluate the motions of water, ions, small molecules, and macromolecules or more complex systems, for example, whole viruses, to reproduce the behavior of the biological environment, including water molecules and lipid membranes. Specifically, structural motions, such as those that are dependent of the temperature and solute/ solvent are very important to study the recognition pattern of ligandprotein or protein-protein complexes, in that sense, MD simulations are very useful because these motions can be modeled using this methodology. Furthermore, MD simulations for drug design provide insights into the structural cavities required to design novel structures with higher affinity to the target. Also, the employment of MD simulations to drug design can help to refine the three-dimensional (3D) structure of targets in order to obtain a better sampling of the binding poses and more reliable affinity values with better structural advantages, because they incorporate some biological conditions that include structural motions compared to traditional docking procedures. This work analyzes the concepts and applicability of MD simulations for drug design because molecular structural motions are considered, and these help to identify hot spots, decipher structural details in the reported protein sites, as well as to eliminate sites that could be structural artifacts which could be originated from the structural characterization conditions from MD. Moreover, better free energy values for protein ligand recognition can also be obtained, and these can be validated under experimental procedures due to the robustness of the MD simulation methods.

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Using DFT and in silico methods a theoretical study, to verify the spectroscopically characterization, this in addition to determine the anti‐inflammatory activity of a set of eight sulfur derivatives of perezone and isoperezone was performed. In this sense, conformational studies for the target sulfurs were carried out, in order to obtain the corresponding minimum energy structures. Also, the vibrational frequencies analysis, the magnitude of 1H NMR and 13C NMR spectra for perezone, isoperezone, and its sulfur‐derivatives, obtained by the DFT/B3LYP/6‐311++G(d,p) method correlated satisfactorily with the experimental data. Moreover, the calculation of physicochemical properties, and the prediction of the anti‐inflammatory activity, employing both PASS predictor and docking studies towards COX‐2 for the target compounds, showed that Benzy perezone is a good candidate as a therapeutic agent; finally, the anti‐inflammatory activity of Benzy perezone was evaluated in vivo, showing a similar naproxen activity.

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It is well known that the principal biomolecules involved in Alzheimer's disease (AD) are acetylcholinesterase (AChE), acetylcholine (ACh) and the amyloid beta peptide of 42 amino acid residues (Aβ42). ACh plays an important role in human memory and learning, but it is susceptible to hydrolysis by AChE, while the aggregation of Aβ42 forms oligomers and fibrils, which form senile plaques in the brain. The Aβ42 oligomers are able to produce hydrogen peroxide (H2O2), which reacts with metals (Fe(2+), Cu(2+), Cr(3+), Zn(2+), and Cd(2+)) present at high concentrations in the brain of AD patients, generating the hydroxyl radical ((·)OH) via Fenton (FR) and Fenton-like (FLR) reactions. This mechanism generates high levels of free radicals and, hence, oxidative stress, which has been correlated with the generation and progression of AD. Therefore, we have studied in vitro how AChE catalytic activity and ACh levels are affected by the presence of metals (Fe(3+), Cu(2+), Cr(3+), Zn(2+), and Cd(2+)), H2O2 (without Aβ42), and (·) OH radicals produced from FR and FLR. The results showed that the H2O2 and the metals do not modify the AChE catalytic activity, but the (·)OH radical causes a decrease in it. On the other hand, metals, H2O2 and (·)OH radicals, increase the ACh hydrolysis. This finding suggests that when H2O2, the metals and the (·)OH radicals are present, both, the AChE catalytic activity and ACh levels diminish. Furthermore, in the future it may be interesting to study whether these effects are observed when H2O2 is produced directly from Aβ42.