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 ligand-protein 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.

Aflatoxin B₁ (AFB₁) exhibits the most potent mutagenic and carcinogenic activity among aflatoxins. For this reason, AFB₁ is recognized as a human group 1 carcinogen by the International Agency of Research on Cancer. Consequently, it is essential to determine its properties and behavior in different chemical systems. The chemical properties of AFB₁ can be explored using computational chemistry, which has been employed complementarily to experimental investigations. The present review includes in silico studies (semiempirical, Hartree–Fock, DFT, molecular docking, and molecular dynamics) conducted from the first computational study in 1974 to the present (2022). This work was performed, considering the following groups: (a) molecular properties of AFB₁ (structural, energy, solvent effects, ground and the excited state, atomic charges, among others); (b) theoretical investigations of AFB₁ (degradation, quantification, reactivity, among others); (c) molecular interactions with inorganic compounds (Ag⁺, Zn²⁺, and Mg²⁺); (d) molecular interactions with environmentally compounds (clays); and (e) molecular interactions with biological compounds (DNA, enzymes, cyclodextrins, glucans, among others). Accordingly, in this work, we provide to the stakeholder the knowledge of toxicity of types of AFB₁-derivatives, the structure–activity relationships manifested by the bonds between AFB₁ and DNA or proteins, and the types of strategies that have been employed to quantify, detect, and eliminate the AFB₁ molecule.

Myeloperoxidase (MPO) is the most abundant heme protein in neutrophils, and MPO catalyzes hypochlorous acid (HOCl) formation. MPO inhibitors (MPOis) can be used to treat several diseases in which MPO and HOCl levels are elevated. The molecular details of several MPOis have not been extensively studied to elucidate their molecular recognition properties. In addition, it is not known whether MPO has only one binding site or more binding sites for aryl compounds, which would explain its promiscuity properties. Therefore, docking simulations were performed to analyze the MPO binding site recognition using several X-ray structures and snapshots retrieved from molecular dynamics (MD) simulations to simulate the binding of MPO with several known aryl ligands. All of the evaluated ligands were recognized by MPO at the same site, which was identified by the Q-Site Finder as being one of the principal sites and named herein as the “principal binding site” (PBS). The PBS is composed of Q91, H95, F99, R239, E242, F366 and F407. The results indicate that the MPO ligand recognition is mediated by Π-Π interactions with an aromatic cluster (F99, F366, F407 and a heme group), giving rise to high MPO promiscuity. In addition, MD simulations and X-ray crystallography show limited conformational variations in the MPO. In addition, either MPOis or another substrate (tyrosine) reaches the same site, but different interactions were observed. Therefore, the results indicate minor movement in the side chain of the mentioned amino acids that allow ligands to be recognized in the same MPO site with different interactions that are dependent on their chemical structures. Furthermore, docking study samples of several conformations retrieved from the MD simulations showed that ABAH was one of the ligands that always had the same interaction. This result provides potential evidence for hydrazides being very good MPOis.