Do Molecular Fingerprints Identify Diverse Active Drugs in Large-Scale Virtual Screening? (No).

Computational approaches for small-molecule drug discovery now regularly scale to the consideration of libraries containing billions of candidate small molecules. One promising approach to increased the speed of evaluating billion-molecule libraries is to develop succinct representations of each molecule that enable the rapid identification of molecules with similar properties. Molecular fingerprints are thought to provide a mechanism for producing such representations.

The Area Law of Molecular Entropy: Moving beyond Harmonic Approximation.

This article shows that the gas-phase entropy of molecules is proportional to the area of the molecules, with corrections for the different curvatures of the molecular surface. The ability to estimate gas-phase entropy by the area law also allows us to calculate molecular entropy faster and more accurately than currently popular methods of estimating molecular entropy with harmonic oscillator approximation. The speed and accuracy of our method will open up new possibilities for the explicit inclusion of entropy in various computational biology methods.

Accurate space-group prediction from composition.

Predicting crystal symmetry simply from chemical composition has remained challenging. Several machine-learning approaches can be employed, but the predictive value of popular crystallographic databases is relatively modest due to the paucity of data and uneven distribution across the 230 space groups. In this work, virtually all crystallographic information available to science has been compiled and used to train and test multiple machine-learning models.

A community effort in SARS-CoV-2 drug discovery.

The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against COVID-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors.

FP-MAP: an extensive library of fingerprint-based molecular activity prediction tools.

Discovering new drugs for disease treatment is challenging, requiring a multidisciplinary effort as well as time, and resources. With a view to improving hit discovery and lead compound identification, machine learning (ML) approaches are being increasingly used in the decision-making process. Although a number of ML-based studies have been published, most studies only report fragments of the wider range of bioactivities wherein each model typically focuses on a particular disease.

Drugsniffer: An Open Source Workflow for Virtually Screening Billions of Molecules for Binding Affinity to Protein Targets.

The SARS-CoV2 pandemic has highlighted the importance of efficient and effective methods for identification of therapeutic drugs, and in particular has laid bare the need for methods that allow exploration of the full diversity of synthesizable small molecules. While classical high-throughput screening methods may consider up to millions of molecules, virtual screening methods hold the promise of enabling appraisal of billions of candidate molecules, thus expanding the search space while concurrently reducing costs and speeding discovery. Here, we describe a new screening pipeline, called , that is capable of rapidly exploring drug candidates from a library of billions of molecules, and is designed to support distributed computation on cluster and cloud resources.

Occurrence of bisphenols and benzophenone UV filters in wild brown mussels (Perna perna) from Algoa Bay in South Africa.

Bisphenols and benzophenone UV filters are contaminants present in a wide variety of plastic materials and consumer products. The scientific attention towards these contaminants has increased in recent years due to their presence in microplastics, their ubiquitous occurrence in the environment, and their known endocrine disrupting health effects. In this study, the occurrence of nine bisphenol and five benzophenone UV-filter analogues was assessed in wild brown mussels (Perna perna) collected from different sampling sites along the coast of Algoa Bay, South Africa.

Systematic assessment of salivary inflammatory markers and dental caries in children: an exploratory study.

Objective: To investigate associations between a wide panel of salivary inflammatory markers and the presence of dental caries among children.

Material And Methods: In this exploratory, cross-sectional study, 176 children, aged 7-9, underwent a dental examination. Information on the children's oral health habits and lifestyles was collected from their mothers.

FP-ADMET: a compendium of fingerprint-based ADMET prediction models.

Motivation: The absorption, distribution, metabolism, excretion, and toxicity (ADMET) of drugs plays a key role in determining which among the potential candidates are to be prioritized. In silico approaches based on machine learning methods are becoming increasing popular, but are nonetheless limited by the availability of data. With a view to making both data and models available to the scientific community, we have developed FPADMET which is a repository of molecular fingerprint-based predictive models for ADMET properties.

Adaptation of central metabolite pools to variations in growth rate and cultivation conditions in Saccharomyces cerevisiae.

Background: Saccharomyces cerevisiae is a well-known popular model system for basic biological studies and serves as a host organism for the heterologous production of commercially interesting small molecules and proteins. The central metabolism is at the core to provide building blocks and energy to support growth and survival in normal situations as well as during exogenous stresses and forced heterologous protein production. Here, we present a comprehensive study of intracellular central metabolite pool profiling when growing S.

Rapid determination of thyroid hormones in blood plasma from Glaucous gulls and Baikal seals by HybridSPE®-LC-MS/MS.

A rapid hybrid solid phase extraction (HybridSPE®) protocol tailored to liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) analysis, was developed for the determination of four thyroid hormones, L-Thyroxine (T), 3,3',5-triiodo-L-thyronine (T), 3,3',5'-triiodo-L-thyronine (rT) and 3,3'-diiodo-L-thyronine (T) in blood plasma from Glaucous gulls (Larus hyperboreus) and Baikal seals (Phoca sibirica). The use of target analyte specific C internal standards allowed quantification to be performed through the standard solvent calibration curves and alleviated the need to perform quantification with matrix match curves. The relative recoveries were 100.

Evaluation of Molecular Fingerprints for Determining Dye Aggregation on Semiconductor Surfaces.

Dye aggregation plays an important role in determining the photovoltaic performance of dye sensitized solar cells. Compared with the spectra observed in solution, it is, apriori, difficult to ascertain whether a dye is likely to show hypsochromic (H) or bathochromic (J) aggregation, until after adsorption onto the semiconductor electrode. Herein, we show that molecular fingerprint-based methods provide a fast and efficient way to discriminate between H- and J-aggregating dyes.

Synthesis of Novel 3,6-Dithienyl Diketopyrrolopyrrole Dyes by Direct C‒H Arylation.

Direct C‒H arylation coupling is potentially a more economical and sustainable process than conventional cross-coupling. However, this method has found limited application in the synthesis of organic dyes for dye‒sensitized solar cells. Although direct C‒H arylation is not an universal solution to any cross-coupling reactions, it efficiently complements conventional sp‒sp bond formation and can provide shorter and more efficient routes to diketopyrrolopyrrole dyes.

Chemical assessment of marine sediments in vicinity of Norwegian fish farms - A pilot study.

While aquaculture is growing rapidly all over the world and generating many economic benefits, so have the environmental concerns about the externalities posed by the fish-farming industry. The distribution profiles of organic compounds and inorganic elements were explored in marine surface sediments collected in proximity of two active Norwegian fish farms, Hestøya and Nørholmen (<200-1100 m from the perimeter edge of the installations). Overall, the sediment organic matter (SOM) content was 7.

Phthalate metabolites in harbor porpoises (Phocoena phocoena) from Norwegian coastal waters.

The exposure of marine mammals to phthalates has received considerable attention due to the ubiquitous occurrence of these pollutants in the marine environment and their potential adverse health effects. The occurrence of phthalate metabolites is well established in human populations, but data is scarce for marine mammals. In this study, concentrations of 17 phthalate metabolites were determined in liver samples collected from one hundred (n = 100) by-caught harbor porpoises (Phocoena phocoena) along the coast of Norway.

Highly efficient cellulose dissolution by alkaline ionic liquids.

Alkaline ionic liquids (ILs) with unconventional organic anions were prepared and used for cellulose dissolution studies. High concentrations of cellulose were dissolved at room temperature in the phenolate based imidazolium IL [Cmim][OPh], combined with organic solvent, and up to 45 wt-% cellulose dissolution (wt-% MCC of weight IL) was readily achieved at 100 ºC. No functionalization of the regenerated cellulose was observed during the dissolution process (FTIR).

Prediction of Absorption Spectrum Shifts in Dyes Adsorbed on Titania.

Dye adsorption on metal-oxide films often results in small to substantial absorption shifts relative to the solution phase, with undesirable consequences for the performance of dye-sensitized solar cells and optical sensors. While density functional theory is frequently used to model such behaviour, it is too time-consuming for rapid assessment. In this paper, we explore the use of supervised machine learning to predict whether dye adsorption on titania is likely to induce a change in its absorption characteristics.

Hydroxyl Functionalized Pyridinium Ionic Liquids: Experimental and Theoretical Study on Physicochemical and Electrochemical Properties.

Structurally modified hydroxyl functionalized pyridinium ionic liquids (ILs), liquid at room temperature, were synthesized and characterized. Alkylated -(2-hydroxyethyl)-pyridinium ILs were prepared from alkylpyridines via corresponding bromide salts by -alkylation (65-93%) and final anion exchange (75-96%). Pyridinium-alkylation strongly influenced the IL physicochemical and electrochemical properties.

Establishing Predictive Models for Solvatochromic Parameters of Ionic Liquids.

The use of ionic liquids (ILs) in applications ranging from catalysis to reaction media in organic synthesis has been successfully demonstrated in several cases. For any given IL application, fundamental properties, such as viscosity, thermal stability, and toxicity have to be considered. Another property of interest is the polarity, which is a crucial indicator of solvent effects on chemical processes.

DENOPTIM: Software for Computational Design of Organic and Inorganic Molecules.

A general-purpose software package, termed DE Novo OPTimization of In/organic Molecules (DENOPTIM), for design and virtual screening of functional molecules is described. Molecules of any element and kind, including metastable species and transition states, are handled as chemical objects that go beyond valence-rules representations. Synthetic accessibility of the generated molecules is ensured via detailed control of the kinds of bonds that are allowed to form in the automated molecular building process.

Benzotriazoles, benzothiazoles and trace elements in an urban road setting in Trondheim, Norway: Re-visiting the chemical markers of traffic pollution.

Road traffic emissions are known to contribute heavily to the pollution in urban environments. The aim of this study was to establish specific traffic pollution markers in an urban road setting based on the occurrence profiles of benzotriazoles, benzothiazoles and trace elements in road dust and relevant matrices, including airborne particulate matter and core asphalt. Benzotriazoles and benzothiazoles are high-production volume chemicals that are used as complexing and anticorrosive agents for metals, act as vulcanizing accelerators for rubber materials, and possess anti-freezing/anti-icing properties.

Local initiation conditions for water autoionization.

The pH of liquid water is determined by the infrequent process in which water molecules split into short-lived hydroxide and hydronium ions. This reaction is difficult to probe experimentally and challenging to simulate. One of the open questions is whether the local water structure around a slightly stretched OH bond is actually initiating the eventual breakage of this bond or whether this event is driven by a global ordering that involves many water molecules far away from the reaction center.

The dye-sensitized solar cell database.

Background: Dye-sensitized solar cells (DSSCs) have garnered a lot of attention in recent years. The solar energy to power conversion efficiency of a DSSC is influenced by various components of the cell such as the dye, electrolyte, electrodes and additives among others leading to varying experimental configurations. A large number of metal-based and metal-free dye sensitizers have now been reported and tools using such data to indicate new directions for design and development are on the rise.

Designing High-Refractive Index Polymers Using Materials Informatics.

A machine learning strategy is presented for the rapid discovery of new polymeric materials satisfying multiple desirable properties. Of particular interest is the design of high refractive index polymers. Our in silico approach employs a series of quantitative structure⁻property relationship models that facilitate rapid virtual screening of polymers based on relevant properties such as the refractive index, glass transition and thermal decomposition temperatures, and solubility in standard solvents.

KRAKENX: software for the generation of alignment-independent 3D descriptors.

The KRAKENX software calculates a large variety of molecular descriptors based on quantum chemistry computations. The program supports over 2000 three-dimensional descriptors that are calculated from the output of different quantum chemistry packages. The current implementation supports semi-empirical MOPAC-based computations and primarily focuses on orientation-independent descriptors that have been discussed in the literature.