A Primer on 2D Descriptors in Selectivity Modeling for Asymmetric Catalysis.

Machine learning has permeated all fields of research, including chemistry, and is now an integral part of the design of novel compounds with desired properties. In the field of asymmetric catalysis, the preference still lies with models based on a physical understanding of the catalysis phenomenon and the electronic and steric properties of catalysts. However, such models require quantum chemical calculations and are thus limited by their computational cost.

Multi-Instance Learning Approach to the Modeling of Enantioselectivity of Conformationally Flexible Organic Catalysts.

Computational design of chiral organic catalysts for asymmetric synthesis is a promising technology that can significantly reduce the material and human resources required for the preparation of enantiopure compounds. Herein, for the modeling of catalysts' enantioselectivity, we propose to use the multi-instance learning approach accounting for multiple catalyst conformers and requiring neither conformer selection nor their spatial alignment. A catalyst was represented by an ensemble of conformers, each encoded by three-dimesinonal (3D) pmapper descriptors.

Predicting Highly Enantioselective Catalysts Using Tunable Fragment Descriptors.

Catalyst optimization processes typically rely on inductive and qualitative assumptions of chemists based on screening data. While machine learning models using molecular properties or calculated 3D structures enable quantitative data evaluation, costly quantum chemical calculations are often required. In contrast, readily available binary fingerprint descriptors are time- and cost-efficient, but their predictive performance remains insufficient.

CGRdb2.0: A Python Database Management System for Molecules, Reactions, and Chemical Data.

This work introduces CGRdb2.0─an open-source database management system for molecules, reactions, and chemical data. CGRdb2.

Atom-to-atom Mapping: A Benchmarking Study of Popular Mapping Algorithms and Consensus Strategies.

In this paper, we compare the most popular Atom-to-Atom Mapping (AAM) tools: ChemAxon, Indigo, RDTool, NameRXN (NextMove), and RXNMapper which implement different AAM algorithms. An open-source RDTool program was optimized, and its modified version ("new RDTool") was considered together with several consensus mapping strategies. The Condensed Graph of Reaction approach was used to calculate chemical distances and develop the "AAM fixer" algorithm for an automatized correction of erroneous mapping.

Reaction Data Curation I: Chemical Structures and Transformations Standardization.

The quality of experimental data for chemical reactions is a critical consideration for any reaction-driven study. However, the curation of reaction data has not been extensively discussed in the literature so far. Here, we suggest a 4 steps protocol that includes the curation of individual structures (reactants and products), chemical transformations, reaction conditions and endpoints.

Discovery of novel chemical reactions by deep generative recurrent neural network.

The "creativity" of Artificial Intelligence (AI) in terms of generating de novo molecular structures opened a novel paradigm in compound design, weaknesses (stability & feasibility issues of such structures) notwithstanding. Here we show that "creative" AI may be as successfully taught to enumerate novel chemical reactions that are stoichiometrically coherent. Furthermore, when coupled to reaction space cartography, de novo reaction design may be focused on the desired reaction class.

Combined Graph/Relational Database Management System for Calculated Chemical Reaction Pathway Data.

Presently, quantum chemical calculations are widely used to generate extensive data sets for machine learning applications; however, generally, these sets only include information on equilibrium structures and some close conformers. Exploration of potential energy surfaces provides important information on ground and transition states, but analysis of such data is complicated due to the number of possible reaction pathways. Here, we present RePathDB, a database system for managing 3D structural data for both ground and transition states resulting from quantum chemical calculations.

Predicting Synergism of Cancer Drug Combinations Using NCI-ALMANAC Data.

Drug combinations are of great interest for cancer treatment. Unfortunately, the discovery of synergistic combinations by purely experimental means is only feasible on small sets of drugs. modeling methods can substantially widen this search by providing tools able to predict which of all possible combinations in a large compound library are synergistic.

Classical scoring functions for docking are unable to exploit large volumes of structural and interaction data.

Motivation: Studies have shown that the accuracy of random forest (RF)-based scoring functions (SFs), such as RF-Score-v3, increases with more training samples, whereas that of classical SFs, such as X-Score, does not. Nevertheless, the impact of the similarity between training and test samples on this matter has not been studied in a systematic manner. It is therefore unclear how these SFs would perform when only trained on protein-ligand complexes that are highly dissimilar or highly similar to the test set.

AntiMalarial Mode of Action (AMMA) Database: Data Selection, Verification and Chemical Space Analysis.

This paper presents the effort of collecting and curating a data set of 15461 molecules tested against the malaria parasite, with robust activity and mode of action annotations. The set is compiled from in-house experimental data and the public ChEMBL database subsets. We illustrate the usefulness of the dataset by building QSAR models for antimalarial activity and QSPR models for modes of actions, as well as by the analysis of the chemical space with the Generative Topographic Mapping method.

QSAR modeling and chemical space analysis of antimalarial compounds.

Generative topographic mapping (GTM) has been used to visualize and analyze the chemical space of antimalarial compounds as well as to build predictive models linking structure of molecules with their antimalarial activity. For this, a database, including ~3000 molecules tested in one or several of 17 anti-Plasmodium activity assessment protocols, has been compiled by assembling experimental data from in-house and ChEMBL databases. GTM classification models built on subsets corresponding to individual bioassays perform similarly to the earlier reported SVM models.

Redox Polypharmacology as an Emerging Strategy to Combat Malarial Parasites.

3-Benzylmenadiones are potent antimalarial agents that are thought to act through their 3-benzoylmenadione metabolites as redox cyclers of two essential targets: the NADPH-dependent glutathione reductases (GRs) of Plasmodium-parasitized erythrocytes and methemoglobin. Their physicochemical properties were characterized in a coupled assay using both targets and modeled with QSPR predictive tools built in house. The substitution pattern of the west/east aromatic parts that controls the oxidant character of the electrophore was highlighted and accurately predicted by QSPR models.

Mappability of drug-like space: towards a polypharmacologically competent map of drug-relevant compounds.

Intuitive, visual rendering--mapping--of high-dimensional chemical spaces (CS), is an important topic in chemoinformatics. Such maps were so far dedicated to specific compound collections--either limited series of known activities, or large, even exhaustive enumerations of molecules, but without associated property data. Typically, they were challenged to answer some classification problem with respect to those same molecules, admired for their aesthetical virtues and then forgotten--because they were set-specific constructs.

Electrochemical properties of substituted 2-methyl-1,4-naphthoquinones: redox behavior predictions.

In the context of the investigation of drug-induced oxidative stress in parasitic cells, electrochemical properties of a focused library of polysubstituted menadione derivatives were studied by cyclic voltammetry. These values were used, together with compatible measurements from literature (quinones and related compounds), to build and evaluate a predictive structure-redox potential model (quantitative structure-property relationship, QSPR). Able to provide an online evaluation (through Web interface) of the oxidant character of quinones, the model is aimed to help chemists targeting their synthetic efforts towards analogues of desired redox properties.

[Mobbing as the syndrome of destructive professiogenesis].

Mobbing has entered reference books as the syndrome including harassment and insult of employees in the workplaces for the purpose of constraint for dismissal. In the framework of the synergetic methodology, fractal dynamics of mobbing sociogenesis, psychogenesis and somatogenesis have been separated. Approaches to early diagnostics and prevention in the framework of the strategies of adaptive professiogenesis formation have been explained.

[Philippe Pinel and the psychiatry of late XVII--early XIX centuries].

The article analyzes the social economic premises promoting the psychiatry to distinguish to independent medical specialty with its own ideological base and methodological filling. The ideological concepts and methodological priorities of psychiatry prevailing in this epoch using the example of views of F. Pinel, his disciples and contemporaries are considered.

[Phenomenon of occupational deformation of personality nowadays].

The authors analyzed destructive features of occupational development, presented main components of destructive development of specialists and professionals, justified synergetic concept of destructive professiogenesis.

[The interdisciplinary approach to the history of psychiatry].

The historical approach is applied ever often to investigate various problems of medicine. The specificity of methodological approach to the history of psychiatry is related with the necessity to implement the historic methods of study not only medicine but other disciplines (non-medical ones included) and the needs of society the progress of medicine depended. The study of problem in this context demands the implementation of the interdisciplinary system to provide the complimentary methodological approach to more comprehensive understanding of historical patterns of development of science and its perspectives.

[A screening procedure for health factors].

A health environment screening procedure has been developed, which is a questionnaire assessing the significance of factors, such as lifestyle, habitat, genetics, public health care, mentality. The developed procedure can ascertain the contribution of each factor to the health of man or a group of individuals, thus defining the factors that may cause diseases, optimize, and individualize the organization of prophylactic care.

Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: a pilot study.

The effects of chronic alcohol consumption on the bowel flora and the potential therapeutic role of probiotics in alcohol-induced liver injury have not previously been evaluated. In this study, 66 adult Russian males admitted to a psychiatric hospital with a diagnosis of alcoholic psychosis were enrolled in a prospective, randomized, clinical trial to study the effects of alcohol and probiotics on the bowel flora and alcohol-induced liver injury. Patients were randomized to receive 5 days of Bifidobacterium bifidum and Lactobacillus plantarum 8PA3 versus standard therapy alone (abstinence plus vitamins).

[The burnout syndrome in communicative professional workers].

To study the specific features of the burnout syndrome (BOS) in communicative professional workers, the authors examined 138 communicative workers (94 females and 44 males); of them there were 51 physical education masters, 43 elementary school teachers, 20 consulting shop assistants, and 24 legal officers. BOS was detected in more than two thirds of elementary school teachers and more than a third of physical education masters, consulting shop assistants, legal officers, and practitioners. The completely developed BOS was most frequently encountered in elementary school teachers (in every four individuals), slightly less frequently in practitioners, consulting shop assistants, and legal officers (in every ten persons).

Ethnic medicine: from fundamental studies to practice of health preservation of the indigenous peoples in the North.

Objectives: We carry out social-hygienic and medical examinations of the indigenous population of the Russian northern territories.

Study Design: Mobile medical teams examined the population of the most of settlements of the Nenets autonomous area.

Methods: The study of the peculiarities of the public health state of the indigenous people.

[Special features of mental and somatic status of the employees of law-enforcement bodies of the Chechen Republic].

With the purpose of study of features of psychical and somatic prosperity of employees of organs of internal affairs of Chechen Republic the inspection of 64 employees was conducted. It is set that a posttraumatic stress disorder (PTSR) was exposed for 3% inspected employees-contracters. The separate symptoms of PTSR were observed for 2/5 contracters and at 1/4 workings on permanent basis.

[The quality of type 1 diabetes management and the internal picture of the disease].

Ninety patients (46 males and 44 females) were examined to study the relationship of the quality of type 1 diabetes melhtus (DM1) management to the clinical picture of the disease (CPD). The examination involved the psychological test "Disease attitudes" and physiobiochemical blood studies. The quality of DM1 management was ascertained to depend on CPD.