In 2016, one of the two enzymes involved in the polyethylene terephthalate (PET) degradation pathway of Ideonella sakaiensis 201-F6, MHETase, was found to exhibit a strong ability to degrade the PET monomer mono-(2-hydroxyethyl)­terephthalate (MHET) at room temperature, converting it back into the precursors used in PET production. MHETase engineering to improve efficiency is an active field that suffers from an incomplete characterization of its reaction mechanism. In this paper, we analyze the reaction mechanism of MHETase using umbrella sampling molecular dynamics simulations at the B3LYP/MM level of theory. The combination of a high theoretical level and extensive sampling generated a very robust computational prediction. We found that MHETase catalyzed the conversion of MHET in two steps, with a rate-limiting step activation barrier of ΔG ⧧ = 19.35 ± 0.15 kcal·mol–1 (from the weighted-histogram analysis). Our calculations are in line with the hypothesis that a transient tetrahedral intermediate mediates the reaction mechanism in each step, which is quite common in the serine hydrolase class. The energy of the first tetrahedral intermediate was similar to that of the reactant state, while the tetrahedral intermediate of the deacylation step was observed to lie closer to the rate-limiting transition state. Nevertheless, both determined tetrahedral states were found to be transient, with activation barriers close to ∼2.0 kcal·mol–1 relative to the product state of the acylation and deacylation steps, corresponding to a half-life of about 3 ps at 303.15 K.

Specialized pro-resolving lipid mediators (SPMs) are natural bioactive agents actively involved in inflammation resolution. SPMs act when uncontrolled inflammatory processes are developed, for instance, in patients of COVID-19 or other...

Since their discovery, carbon nanotubes and other related nanomaterials are in the spotlight due to their unique molecular structures and properties, having a wide range of applications. The cage-like structure of carbon nanotubes is especially appealing as a route to confine molecules, isolating them from the solvent medium. This study aims to explore and characterize, through density functional theory (DFT) calculations, covalent tip-functionalization of single-walled carbon nanotubes (SWCNTS) with carboxymethyl moieties that establish pH sensitive molecular gates. The response of the molecular gate to pH fluctuations arises from variations in the noncovalent interactions between functionalized groups, which depend on the extent of protonation, leading to conformational changes. Overall, the hydrogen bonds present in the molecular models under study, as evaluated through topological analysis and pK a calculations, suggest that functionalized SWCNTs may be suitable for the design of drug delivery systems to enhance the efficiency of some pharmacological treatments, or even in the area of catalysis and separation processes, through their incorporation in nanocomposites.

No abstract

Graphene oxide (GO), a nanomaterial with promising applications that range from water purification to enzyme immobilization, is actively present in scientific research since its discovery. GO studies with computational methodologies such as molecular dynamics are frequently reported in the literature; however, the models used often rely on approximations, such as randomly placing functional groups and the use of generalized force fields. Therefore, it is important to develop new MD models that provide a more accurate description of GO structures and their interaction with an aqueous solvent and other adsorbate molecules. In this paper, we derived new force field non-bonded parameters from linear-scaling density functional theory calculations of nanoscale GO sheets with more than 10,000 atoms through an atoms-in-molecules (AIM) partitioning scheme. The resulting GAFF2-AIM force field, derived from the bonded terms of GAFF2 parameterization, reproduces the solvent structure reported in ab initio MD simulations better than the force field nowadays widely used in the literature. Additionally, we analyzed the effect of the ionic strength of the medium and of the C/O ratio on the distribution of charges surrounding the GO sheets. Finally, we simulated the adsorption of natural amino acid molecules to a GO sheet and estimated their free energy of binding, which compared very favorably to their respective experimental values, validating the force field presented in this work.