Structure and Energetics of PET-Hydrolyzing Enzyme Complexes: A Systematic Comparison from Molecular Dynamics Simulations.

Discovered in 2016, the enzyme PETase, secreted by bacterial 201-F6, has an excellent hydrolytic activity toward poly(ethylene terephthalate) (PET) at room temperature, while it decreases at higher temperatures due to the low thermostability. Many variants have been engineered to overcome this limitation, which hinders industrial application. In this work, we systematically compare PETase wild-type (WT) and four mutants (DuraPETase, ThermoPETase, FastPETase, and HotPETase) using standard molecular dynamics (MD) simulations and unbinding free energy calculations.

Blueshift of the CN stretching vibration of acetonitrile in solution: computational and experimental study.

Acetonitrile, a polar molecule that cannot form hydrogen bonds on its own, interacts with solvent molecules mainly through the lone pair of its nitrogen atom and the π electrons of its CN triple bond [Correction added on 17 July 2024, after first online publication: Acetole has been changed to Acetonitrile in the preceeding sentence.]. Interestingly, acetonitrile exhibits an unexpected strengthening of the triple bond's force constant in an aqueous environment, leading to an upshift (blueshift) in the corresponding stretching vibration: this effect contrasts with the usual consequence of hydrogen bonding on the vibrational frequencies of the acceptor groups, that is, frequency redshift.

Quantum-Chemistry Study of the Hydrolysis Reaction Profile in Borate Networks: A Benchmark.

This investigation involved an ab initio and Density Functional Theory (DFT) analysis of the hydrolysis mechanism and energetics in a borate network. The focus was on understanding how water molecules interact with and disrupt the borate network, an area where the experimental data are scarce and unreliable. The modeled system consisted of two boron atoms, bridging oxygen atoms, and varying numbers of water molecules.

Evidence of Multiple Crystallization Pathways in Lithium Disilicate: A Metadynamics Investigation.

Metadynamics simulations driven by using two X-ray diffraction peaks identified three alternative crystallization pathways of the lithium disilicate crystal from the melt. The most favorable one passes through the formation of disordered layered structures undergoing internal ordering in a second step. The second pathway involves the formation of phase-separated structures composed of nuclei of β-cristobalite crystals surrounded by lithium-rich phases in which metasilicate chains are formed.

Can DFT Calculations Provide Useful Information for SERS Applications?

Density functional theory (DFT) calculations allow us to reproduce the SERS (surface-enhanced Raman scattering) spectra of molecules adsorbed on nanostructured metal surfaces and extract the most information this spectroscopy is potentially able to provide. The latter point mainly concerns the anchoring mechanism and the bond strength between molecule and metal as well as the structural and electronic modifications of the adsorbed molecule. These findings are of fundamental importance for the application of this spectroscopic technique.

Alginate Beads Containing Cerium-Doped Mesoporous Glass and Curcumin: Delivery and Stabilization of Therapeutics.

Cancer is a leading cause of death worldwide, its genesis and progression are caused by homeostatic errors, and reactive oxygen species play a major role in promoting aberrant cancer homeostasis. In this scenario, curcumin could be an interesting candidate due to its versatile antioxidant, anti-inflammatory, anti-tumor, anti-HIV, and anti-infection properties. Nonetheless, the major problem related to its use is its poor oral bioavailability, which can be overcome by encapsulating it into small particles, such as hydrogel beads containing mesoporous silica.

DFT and TD-DFT Study of the Chemical Effect in the SERS Spectra of Piperidine Adsorbed on Silver Colloidal Nanoparticles.

The surface-enhanced Raman scattering (SERS) spectra of piperidine adsorbed on silver/chloride colloids were studied by a combined density functional theory (DFT)/time dependent DFT (TD-DFT) approach. The mechanism of chemical enhancement on the Raman signals is due to at least two contributions: the first comes from the changes in the molecular force constants and the dynamic polarizabilities of the normal modes, when the molecule is chemisorbed. DFT calculations satisfactorily reproduce the SERS spectra of piperidine adsorbed on silver, showing that the species formed on the silver particle is a complex formed by a deprotonated piperidine linked to a silver cation.

Biasing crystallization in fused silica: An assessment of optimal metadynamics parameters.

Metadynamics (MetaD) is a useful technique to study rare events such as crystallization. It has been only recently applied to study nucleation and crystallization in glass-forming liquids such as silicates, but the optimal set of parameters to drive crystallization and obtain converged free energy surfaces is still unexplored. In this work, we systematically investigated the effects of the simulation conditions to efficiently study the thermodynamics and mechanism of crystallization in highly viscous systems.

Computational Insight on the Interaction of Common Blood Proteins with Gold Nanoparticles.

Protein interactions with engineered gold nanoparticles (AuNPs) and the consequent formation of the protein corona are very relevant and poorly understood biological phenomena. The nanoparticle coverage affects protein binding modalities, and the adsorbed protein sites influence interactions with other macromolecules and cells. Here, we studied four common blood proteins, i.

Exploring Translocator Protein (TSPO) Medicinal Chemistry: An Approach for Targeting Radionuclides and Boron Atoms to Mitochondria.

Translocator protein 18 kDa [TSPO or peripheral-type benzodiazepine receptor (PBR)] was identified in the search of binding sites for benzodiazepine anxiolytic drugs in peripheral regions. In these areas, binding sites for TSPO ligands were recognized in steroid-producing tissues. TSPO plays an important role in many cellular functions, and its coding sequence is highly conserved across species.

Development and Application of a ReaxFF Reactive Force Field for Cerium Oxide/Water Interfaces.

Ceria (CeO) is a well-known catalytic oxide with many environmental, energy production, and industrial applications, most of them involving water as a reactant, byproduct, solvent, or simple spectator. In this work, we parameterized a Ce/O/H ReaxFF for the study of ceria and ceria/water interfaces. The parameters were fitted to an training set obtained at the DFT/PBE0 level, including the structures, cohesive energies, and elastic properties of the crystalline phases Ce, CeO, and CeO; the O-defective structures and energies of vacancy formation on CeO bulk and CeO (111) surface, as well as the absorption and reaction energies of H and HO molecules on CeO (111).

Novel Pet-Degrading Enzymes: Structure-Function from a Computational Perspective.

The bacterium strain Ideonella sakaiensis 201-F6 is able to hydrolyze low-crystallinity PET films at 30 °C due to two enzymes named PETase and MHETase. Since its discovery, many efforts have been dedicated to elucidating the structure and features of those two enzymes, and various authors have highlighted the necessity to optimize both the substrate binding site and the global structure in order to enhance the stability and catalytic activity of these PET biocatalysts so as to make them more suitable for industrial applications. In this review, the strategies adopted by different research groups to investigate the structure and functionality of both PETase and MHETase in depth are described, emphasizing the advantages provided by the use of computational methods to complement and drive experiments.

Disclosing the Interaction of Gold Nanoparticles with Aβ(1-40) Monomers through Replica Exchange Molecular Dynamics Simulations.

Amyloid-β aggregation is one of the principal causes of amyloidogenic diseases that lead to the loss of neuronal cells and to cognitive impairments. The use of gold nanoparticles treating amyloidogenic diseases is a promising approach, because the chemistry of the gold surface can be tuned in order to have a specific binding, obtaining effective tools to control the aggregation. In this paper, we show, by means of Replica Exchange Solute Tempering Molecular Simulations, how electrostatic interactions drive the absorption of Amyloid-β monomers onto citrates-capped gold nanoparticles.

Disclosing crystal nucleation mechanism in lithium disilicate glass through molecular dynamics simulations and free-energy calculations.

Unraveling detailed mechanism of crystal nucleation from amorphous materials is challenging for both experimental and theoretical approaches. In this study, we have examined two methods to understand the initial stage of crystal precipitation from lithium disilicate glasses using molecular dynamics simulations. One of the methods is a modified exploring method to find structurally similar crystalline clusters in the glass models, enabling us to find three different embryos, such as LiSiO (LS), LiSiO (LS) and LiPO (LP), in the 33LiO·66SiO·1PO glass (LSP1), in which PO is added as a nucleating agent.

Computational Insights into the Binding of Monolayer-Capped Gold Nanoparticles onto Amyloid-β Fibrils.

Amyloids-β (Aβ) fibrils are involved in several neurodegenerative diseases. In this study, atomistic molecular dynamics simulations have been used to investigate how monolayer-protected gold nanoparticles interact with Aβ(1-40) and Aβ(1-42) fibrils. Our results show that small gold nanoparticles bind with the external side of amyloid-β fibrils that is involved in the fibrillation process.

Insights into the Effect of Curcumin and (-)-Epigallocatechin-3-Gallate on the Aggregation of Aβ(1-40) Monomers by Means of Molecular Dynamics.

In this study, we compared the effects of two well-known natural compounds on the early step of the fibrillation process of amyloid-β (1-40), responsible for the formation of plaques in the brains of patients affected by Alzheimer's disease (AD). The use of extensive replica exchange simulations up to the µs scale allowed us to characterize the inhibition activity of (-)-epigallocatechin-3-gallate (EGCG) and curcumin (CUR) on unfolded amyloid fibrils. A reduced number of β-strands, characteristic of amyloid fibrils, and an increased distance between the amino acids that are responsible for the intra- and interprotein aggregations are observed.

Unraveling the complexity of amyloid polymorphism using gold nanoparticles and cryo-EM.

Increasing evidence suggests that amyloid polymorphism gives rise to different strains of amyloids with distinct toxicities and pathology-spreading properties. Validating this hypothesis is challenging due to a lack of tools and methods that allow for the direct characterization of amyloid polymorphism in hydrated and complex biological samples. Here, we report on the development of 11-mercapto-1-undecanesulfonate-coated gold nanoparticles (NPs) that efficiently label the edges of synthetic, recombinant, and native amyloid fibrils derived from different amyloidogenic proteins.

Structural origins of the Mixed Alkali Effect in Alkali Aluminosilicate Glasses: Molecular Dynamics Study and its Assessment.

The comprehension of the nonlinear effects provided by mixed alkali effect (MAE) in oxide glasses is useful to optimize glass compositions to achieve specific properties that depend on the mobility of ions, such as the chemical durability, glass transition temperature, viscosity and ionic conductivity. Although molecular dynamics (MD) simulations have already been applied to investigate the MAE on silicates, less effort has been devoted to study such phenomenon in mixed alkali aluminosilicate glasses where alkali cations can act both as modifiers, forming non-bridging oxygens and percolation channels, and as charge compensator of the AlO units present in the network. Moreover, the ionic conductivity has not been computed yet; thus, the accuracy of the atomistic simulations in reproducing the MAE on the property is still open to question.

A DFT Approach to the Surface-Enhanced Raman Scattering of 4-Cyanopyridine Adsorbed on Silver Nanoparticles.

A Surface-Enhanced Raman Scattering (SERS) spectrum of 4-cyanopyridine (4CNPy) was recorded on silver plasmonic nanoparticles and analyzed by using Density Functional Theory (DFT) calculations. Two simple molecular models of the metal-4CNPy surface complex with a single silver cation or with a neutral dimer (Ag-4CNPy, Ag-4CNPy), linked through the two possible interacting sites of 4CNPy (aromatic nitrogen, N, and nitrile group, CN), were considered. The calculated vibrational wavenumbers and intensities of the adsorbate and the isolated species are compared with the experimental Raman and SERS results.

DARPin_9-29-Targeted Mini Gold Nanorods Specifically Eliminate HER2-Overexpressing Cancer Cells.

We have demonstrated that designed ankyrin repeat protein (DARPin) _9-29, which specifically targets human epidermal growth factor receptor 2 (HER2), binds tightly to gold mini nanorods (GNRs). Molecular dynamic simulations showed that a single layer of DARPin_9-29 molecules is formed on the surface of the nanorod and that conjugation with the nanorod does not involve the protein's domain responsible for specific binding to HER2. The nanorod-DARPin (DARPin-GNR) conjugate is specifically bound (in nanomolar concentrations) to human breast adenocarcinoma SK-BR-3 cells overexpressing HER2.

Multiscale Molecular Dynamics Simulation of Multiple Protein Adsorption on Gold Nanoparticles.

A multiscale molecular dynamics simulation study has been carried out in order to provide in-depth information on the adsorption of hemoglobin, myoglobin, and trypsin over citrate-capped AuNPs of 15 nm diameter. In particular, determinants for single proteins adsorption and simultaneous adsorption of the three types of proteins considered have been studied by Coarse-Grained and Meso-Scale molecular simulations, respectively. The results, discussed in the light of the controversial experimental data reported in the current experimental literature, have provided a detailed description of the (i) recognition process, (ii) number of proteins involved in the early stages of corona formation, (iii) protein competition for AuNP adsorption, (iv) interaction modalities between AuNP and protein binding sites, and (v) protein structural preservation and alteration.

Assessment of Density Functional Approximations for Highly Correlated Oxides: The Case of CeO and CeO.

CeO based materials are very attractive as catalytic components for industrial processes and environmentally friendly technologies; therefore, a reliable and computationally affordable theoretical description of the main properties of ceria is needed. In particular, the description of the interconversion between the Ce(IV) and Ce(III) oxidation states, on which lies the main chemical features of the cerium oxide, results in quite a challenge at the Density Functional Theory level. Here, we tested several density functional approximations, spanning from GGA to hybrid (Global, Meta-Global, and Range Separated Corrected) functionals, on the structural, vibrational, electronic, and thermochemical properties of bulk CeO and CeO.

Curcumin derivatives and Aβ-fibrillar aggregates: An interactions' study for diagnostic/therapeutic purposes in neurodegenerative diseases.

Several neurodegenerative diseases, like Alzheimer's (AD), are characterized by amyloid fibrillar deposition of misfolded proteins, and this feature can be exploited for both diagnosis and therapy design. In this paper, structural modifications of curcumin scaffold were examined in order to improve its bioavailability and stability in physiological conditions, as well as its ability to interfere with β-amyloid fibrils and aggregates. The acid-base behaviour of curcumin derivatives, their pharmacokinetic stability in physiological conditions, and in vitro ability to interfere with Aβ fibrils at different incubation time were investigated.

Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1⁻40) Fibrils.

One of the principal hallmarks of Alzheimer's disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists of either blocking the amyloid aggregation and/or destroying the already formed aggregates. Natural products have shown significant therapeutic potential as amyloid inhibitors from in vitro studies as well as in vivo animal tests.

Computational Insight into the Interaction of Cytochrome C with Wet and PVP-Coated Ag Surfaces.

In this work, the adsorption of cytochrome C (CytC) on wet {100}, {111}, {110}, and {120} silver surfaces has been investigated by computational simulations. The effect of polyvinylpyrrolidone (PVP) coating has also been studied. The main results obtained can be summarized as follow: (a) CytC strongly interacts with wet bare high index facets, while the adsorption over the {100} surface is disfavored due to the strong water structuring at the surface; (b) a nonselective protein adsorption mechanism is highlighted; (c) the native structure of CytC is well preserved during adsorption; (d) the heme group of CytC is never found to interact directly with the surface; (e) the interactions with the PVP-capped {100} surface is weak and specific.