Accelerating molecular Monte Carlo simulations using distance and orientation-dependent energy tables: tuning from atomistic accuracy to smoothed "coarse-grained" models

Typically, the most time consuming part of any atomistic molecular simulation is the repeated calculation of distances, energies, and forces between pairs of atoms. However, many molecules contain nearly rigid multi-atom groups such as rings and other conjugated moieties, whose rigidity can be exploited to significantly speed-up computations. The availability of GB-scale random-access memory (RAM) offers the possibility of tabulation (precalculation) of distance- and orientation-dependent interactions among such rigid molecular bodies. Here, we perform an investigation of this energy tabulation approach for a fluid of atomistic-but rigid-benzene molecules at standard temperature and density. In particular, using O(1) GB of RAM, we construct an energy look-up table, which encompasses the full range of allowed relative positions and orientations between a pair of whole molecules. We obtain a hardware-dependent speed-up of a factor of 24-50 as compared to an ordinary ("exact") Monte Carlo simulation and find excellent agreement between energetic and structural properties. Second, we examine the somewhat reduced fidelity of results obtained using energy tables based on much less memory use. Third, the energy table serves as a convenient platform to explore potential energy smoothing techniques, akin to coarse-graining. Simulations with smoothed tables exhibit near atomistic accuracy while increasing diffusivity. The combined speed-up in sampling from tabulation and smoothing exceeds a factor of 100. For future applications, greater speed-ups can be expected for larger rigid groups, such as those found in biomolecules.     

Continuous Succinic Acid Fermentation by Actinobacillus Succinogenes: Assessment of Growth and Succinic Acid Production Kinetics

Applied Biochemistry and Biotechnology - Succinic acid is one of the most interesting platform chemicals that can be produced in a biorefinery approach. The paper reports the characterization of...     

Metabolite profiling of licorice (Glycyrrhiza glabra) from different locations using comprehensive two-dimensional liquid chromatography coupled to diode array and tandem mass spectrometry detection

Profiling of the main metabolites from several licorice (Glycyrrhiza glabra) samples collected at different locations is carried out in this work by using comprehensive two-dimensional liquid chromatography (LC × LC) coupled to diode array (DAD) and mass spectrometry (MS) detectors. The optimized method was based on the application of a HILIC-based separation in the first dimension combined with fast RP-based second dimension separation. This set-up was shown to possess powerful separation capabilities allowing separating as much as 89 different metabolites in a single sample. Identification and grouping of metabolites according to their chemical class were achieved using the DAD, MS and MS/MS data. Triterpene saponins were the most abundant metabolites followed by glycosylated flavanones and chalcones, whereas glycyrrhizic acid, as expected, was confirmed as the main component in all the studied samples. LC × LC-DAD-MS/MS was able to resolve these complex licorice samples providing with specific metabolite profiles to the different licorice samples depending on their geographical origin. Namely, from 19 to 50 specific compounds were exclusively determined in the 2D-chromatograms from the different licorice samples depending on their geographical origin, which can be used as a typical pattern that could potentially be related to their geographical location and authentication.     

Investigation of thermal transport in n-type porous silicon by photo-acoustic technique

Non-destructive thermal and optical characterization of materials can be successfully performed by the photo-acoustic technique. In this work, this technique has been applied to the measure of thermal conductivity in porous silicon by considering the photo-acoustic response at fixed frequency of samples having the same porosity but different thicknesses. Experimental data are interpreted in terms of a model which takes into account both scattering effects and the contribution to the photo-acoustic signal of the interstitial gas expansion. The measured thermal conductivity is found to be lower than the one reported for crystalline silicon by two orders of magnitude. A discussion of the photo-acoustic signal dependence on the morphology of the porous medium is also presented.     

A Reversible and Selective Inhibitor of Monoacylglycerol Lipase Ameliorates Multiple Sclerosis

Monoacylglycerol lipase (MAGL) is the enzyme responsible for the inactivation of the endocannabinoid 2‐arachidonoylglycerol (2‐AG). MAGL inhibitors show analgesic and tissue‐protecting effects in several disease models. However, the few efficient and selective MAGL inhibitors described to date block the enzyme irreversibly, and this can lead to pharmacological tolerance. Hence, additional classes of MAGL inhibitors are needed to validate this enzyme as a therapeutic target. Here we report a potent, selective, and reversible MAGL inhibitor (IC₅₀=0.18 μM ) which is active in vivo and ameliorates the clinical progression of a multiple sclerosis (MS) mouse model without inducing undesirable CB₁‐mediated side effects. These results support the interest in MAGL as a target for the treatment of MS.     

Evaluation of molecularly imprinted polymers using 2′,3′,5′-tri-O-acyluridines as templates for pyrimidine nucleoside recognition

In this paper, we describe the synthesis and evaluation of molecularly imprinted polymers (MIPs), prepared using 2′,3′,5′-tri-O-acyluridines as ‘dummy’ templates, for the selective recognition of uridine nucleosides. The MIPs were synthesised using a non-covalent approach with 2,6-bis-acrylamidopyridine (BAAPy) acting as the binding monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linking agent. The MIPs were evaluated in terms of capacity, selectivity and specificity by analytical and frontal liquid chromatography measurements. The results obtained in organic mobile phases suggest that the nucleosides are specifically bound to the polymer by the complementary hydrogen bonding motifs of the binding monomer and the nucleoside bases. The MIPs exhibited relatively high imprinting factors for 2′,3′,5′-tri-O-acyluridines, while they did not show any binding capacity for other nucleosides lacking the imide moiety on their base. Moreover, the presence of ester-COO groups in the EGDMA cross-linker may lead to the formation of additional hydrogen bonds with the 2′,3′ and/or 5′-OH of sugar part, allowing enhancement of the recognition of the uridine nucleosides. In aqueous media, results show that the binding is driven by hydrophobic interactions.     

Natural Product-Based Hybrids as Potential Candidates for the Treatment of Cancer: Focus on Curcumin and Resveratrol

One of the main current strategies for cancer treatment is represented by combination chemotherapy. More recently, this strategy shifted to the “hybrid strategy”, namely the designing of a new molecular entity containing two or more biologically active molecules and having superior features compared with the individual components. Moreover, the term “hybrid” has further extended to innovative drug delivery systems based on biocompatible nanomaterials and able to deliver one or more drugs to specific tissues or cells. At the same time, there is an increased interest in plant-derived polyphenols used as antitumoral drugs. The present review reports the most recent and intriguing research advances in the development of hybrids based on the polyphenols curcumin and resveratrol, which are known to act as multifunctional agents. We focused on two issues that are particularly interesting for the innovative chemical strategy involved in their development. On one hand, the pharmacophoric groups of these compounds have been used for the synthesis of new hybrid molecules. On the other hand, these polyphenols have been introduced into hybrid nanomaterials based on gold nanoparticles, which have many potential applications for both drug delivery and theranostics in chemotherapy.     

Nano- and femtosecond UV laser pulses to immobilize biomolecules onto surfaces with preferential orientation

By relying on the photonic immobilization technique of antibodies onto surfaces, we realized portable biosensors for light molecules based on the use of quartz crystal microbalances, given the linear dependence of the method on the laser pulse intensity. Here, we compare the quality of the anchoring method when using nanosecond (260 nm, 25 mJ/pulse, 5 ns, 10 Hz rep. rate) and femtosecond (258 nm, 25 μJ/pulse, 150 fs, 10 kHz rep. rate) laser source, delivering the same energy to the sample with the same average power. As a reference, we also tethered untreated antibodies by means of the passive adsorption. The results are striking: When the antibodies are irradiated with the femtosecond pulses, the deposition on the gold plate is much more ordered than in the other two cases. The effects of UV pulses irradiation onto the antibodies are also analyzed by measuring absorption and fluorescence and suggest the occurrence of remarkable degradation when nanosecond pulses are used likely induced by a larger thermal coupling. In view of the high average power required to activate the antibodies for the achievement of the photonic immobilization technique, we conclude that femtosecond rather than nanosecond laser pulses have to be used.