Evaluating the use of absolute binding free energy in the fragment optimization process.

Key to the fragment optimization process is the need to accurately capture the changes in affinity that are associated with a given set of chemical modifications. Due to the weakly binding nature of fragments, this has proven to be a challenging task, despite recent advancements in leveraging experimental and computational methods. In this work, we evaluate the use of Absolute Binding Free Energy (ABFE) calculations in guiding fragment optimization decisions, retrospectively calculating binding free energies for 59 ligands across 4 fragment elaboration campaigns. We first demonstrate that ABFEs can be used to accurately rank fragment-sized binders with an overall Spearman’s r of 0.89 and a Kendall τ of 0.67, although often deviating from experiment in absolute free energy values with an RMSE of 2.75 kcal/mol. We then also show that in several cases, retrospective fragment optimization decisions can be supported by the ABFE calculations. Cases that were not supported were often limited by large uncertainties in the free energy estimates, however generally the right direction in ΔΔG is still observed. Comparing against cheaper endpoint methods, namely Nwat-MM/GBSA, we find that ABFEs offer better outcomes in ranking binders, improving correlation metrics, although a similar confidence in retrospective synthetic decisions is achieved. Our results indicate that ABFE calculations are currently at the level of accuracy that can be usefully employed to gauge which fragment elaborations are likely to offer the best gains in affinity.

Conventional agrochemicals towards nano-biopesticides: an overview on recent advances

Pesticides are classified into several groups based on their structure, including fungicides, insecticides, herbicides, bactericides, and rodenticides. Pesticides are toxic to both humans and pests. For pest control, a very small amount of pesticides reach their target pests. Therefore, nearly all pesticides move through the environment and exert adverse effects on beneficial biota and public health. These chemicals pollute the water, soil, and atmosphere of the ecosystem. Agricultural workers in greenhouses and open fields, exterminators of house pests, and workers in the pesticide industry are occupationally exposed to pesticides. Pesticide exposure in the general population primarily happens through the consumption of food and water contaminated with pesticide residues; however, substantial exposure can also occur outside or inside the house. Currently, intelligent, responsive, biodegradable, and biocompatible materials have attracted considerable interest for the formulation of green, safe, and efficient pesticides. It was indicated that utilizing nanotechnology to design and prepare targeted pesticides with an environmentally responsive controlled release via chemical modifications and compounds offers great potential for creating new formulations. Furthermore, biopesticides include microbial pesticides, which are naturally happening biochemical pesticides. In addition, pesticidal substances generated by plants with added genetic materials, i.e., plant-incorporated protectants (PIPs), have emerged. Based on the foregoing evidence, various types of pesticides are summarized in this review for the first time. Here, new pesticides including nano-pesticides and biopesticides are discussed while focusing on the most recent findings on targeted and safe nano-formulated biopesticides and nano-pesticides. Graphical Abstract

Post-Synthetic Enzymatic and Chemical Modifications for Novel Sustainable Polyesters

Because of their biodegradability, compostability, compatibility and flexible structures, biodegradable polymers such as polyhydroxyalkanoates (PHA) are an important class of biopolymers with various industrial and biological uses. PHAs are thermoplastic polyesters with a limited processability due to their low heat resistance. Furthermore, due to their high crystallinity, some PHAs are stiff and brittle. These features result sometimes in very poor mechanical characteristics with low extension at break values which limit the application range of some natural PHAs. Several in vivo approaches for PHA copolymer modifications range from polymer production to enhance PHA-based material performance after synthesis. The methods for enzymatic and chemical polymer modifications are aiming at modifying the structures of the polyesters and thereby their characteristics while retaining the biodegradability. This survey illustrates the efficient use of enzymes and chemicals in post-synthetic PHA modifications, offering insights on these green techniques for modifying and improving polymer performance. Important studies in this sector will be reviewed, as well as chances and obstacles for their stability and hyper-production.

Fullerene Superlattices Containing Charge Transfer Complexes for Enhanced Nonlinear Optical Performance

To improve the nonlinear optical (NLO) properties of fullerene C60, chemical modifications are normally needed to construct donor-π-acceptor (D-π-A) system, which needs tedious and time-consuming synthetic procedures. In addition, the...

Electronic structures of the MoS2/TiO2 (anatase) heterojunction: influence of physical and chemical modifications at the 2D- or 1D-interfaces

To tackle the challenge of the CO2 photoreduction, semiconducting layered transition metal dichalcogenides like MoS2 have attracted much attention due to their tunable 2D nano-structures. By using advanced periodic density...

Deciphering the tRNA-derived small RNAs: origin, development, and future

Transfer RNA (tRNA)-derived small RNAs (tsRNAs), a novel category of small noncoding RNAs, are enzymatically cleaved from tRNAs. Previous reports have shed some light on the roles of tsRNAs in the development of human diseases. However, our knowledge about tsRNAs is still relatively lacking. In this paper, we review the biogenesis, classification, subcellular localization as well as action mechanism of tsRNAs, and discuss the association between chemical modifications of tRNAs and the production and functions of tsRNAs. Furthermore, using immunity, metabolism, and malignancy as examples, we summarize the molecular mechanisms of tsRNAs in diseases and evaluate the potential of tsRNAs as new biomarkers and therapeutic targets. At the same time, we compile and introduce several resource databases that are currently publicly available for analyzing tsRNAs. Finally, we discuss the challenges associated with research in this field and future directions.

A Comprehensive Analysis of the Thrombin Binding Aptamer Containing Functionalized Pyrrolo-2’-deoxycytidines

Aptamers constitute an answer for the growing need for targeted therapy development. One of the most well-known representatives of this group of compounds is thrombin binding aptamers (TBA) targeted towards thrombin. The TBA inhibitory activity is determined by its spatial arrangement, which consists of two G-tetrads linked by two shorter TT loops and one longer TGT loop and folds into a unimolecular, antiparallel G-quadruplex structure. Interesting properties of the aptamer can be further improved via the introduction of a number of chemical modifications. Herein, a comprehensive analysis of the influence of pyrrolo-2’-deoxycytidine (Py-dC) and its derivatives on TBA physicochemical and biological properties has been presented. The studies have shown that the presence of modified residues at the T7 position of the TGT loop has only minor effects on TBA thermodynamic stability without affecting its folding topology. All analyzed oligomers exhibit anticoagulant properties, but only aptamer modified with a decyl derivative of Py-dC was able to inhibit thrombin activity more efficiently than unmodified, parental compounds. Importantly, the same compound also possessed the potential to effectively restrain HeLa cell line growth.

Contact transmission of SARS-CoV-2 on fomite surfaces: surface survival and risk reduction

There is an unprecedented concern regarding the viral strain SARS-CoV-2 and especially its respiratory disease more commonly known as COVID-19. SARS-CoV-2 virus has the ability to survive on different surfaces for extended periods, ranging from days up to months. The new infectious properties of SARS-CoV-2 vary depending on the properties of fomite surfaces. In this review, we summarize the risk factors involved in the indirect transmission pathways of SARS-CoV-2 strains on fomite surfaces. The main mode of indirect transmission is the contamination of porous and non-porous inanimate surfaces such as textile surfaces that include clothes and most importantly personal protective equipment like personal protective equipment kits, masks, etc. In the second part of the review, we highlight materials and processes that can actively reduce the SARS-CoV-2 surface contamination pattern and the associated transmission routes. The review also focuses on some general methodologies for designing advanced and effective antiviral surfaces by physical and chemical modifications, viral inhibitors, etc.