Profiling and analysis of chemical compounds using pointwise mutual information

Čmelo, Ivan; Voršilák, Milan; Svozil, Daniel

doi:10.1186/s13321-020-00483-y

Cited by 3 publications

(1 citation statement)

References 61 publications

(104 reference statements)

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“…This algorithm is a complementary (testing) method, very recently employed in chemistry, which measures the structural similarity between compounds by computing the mutual information (from information theory) between the InChIKey codes. Such approaches were recently used to characterize structure similarity [37] and drug-target compatibility [38]. This phase is necessary in order to narrow the search range for a probable mechanism of action characteristic of the studied lupane derivatives.…”

Section: Machine Learning Antitubercular Activity and Compound-drug Similarity Predictionmentioning

confidence: 99%

New Investigations with Lupane Type A-Ring Azepane Triterpenoids for Antimycobacterial Drug Candidate Design

Казакова

Racoviceanu

Petrova

et al. 2021

IJMS

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Twenty lupane type A-ring azepano-triterpenoids were synthesized from betulin and its related derivatives and their antitubercular activity against Mycobacterium tuberculosis, mono-resistant MTB strains, and nontuberculous strains Mycobacterium abscessus and Mycobacterium avium were investigated in the framework of AToMIc (Anti-mycobacterial Target or Mechanism Identification Contract) realized by the Division of Microbiology and Infectious Diseases, NIAID, National Institute of Health. Of all the tested triterpenoids, 17 compounds showed antitubercular activity and 6 compounds were highly active on the H37Rv wild strain (with MIC 0.5 µM for compound 7), out of which 4 derivatives also emerged as highly active compounds on the three mono-resistant MTB strains. Molecular docking corroborated with a machine learning drug-drug similarity algorithm revealed that azepano-triterpenoids have a rifampicin-like antitubercular activity, with compound 7 scoring the highest as a potential M. tuberculosis RNAP potential inhibitor. FIC testing demonstrated an additive effect of compound 7 when combined with rifampin, isoniazid and ethambutol. Most compounds were highly active against M. avium with compound 14 recording the same MIC value as the control rifampicin (0.0625 µM). The antitubercular ex vivo effectiveness of the tested compounds on THP-1 infected macrophages is correlated with their increased cell permeability. The tested triterpenoids also exhibit low cytotoxicity and do not induce antibacterial resistance in MTB strains.

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Section: Machine Learning Antitubercular Activity and Compound-drug Similarity Predictionmentioning

confidence: 99%

New Investigations with Lupane Type A-Ring Azepane Triterpenoids for Antimycobacterial Drug Candidate Design

Казакова

Racoviceanu

Petrova

et al. 2021

IJMS

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Turning high-throughput structural biology into predictive inhibitor design

Saar

Fearon

Delft³

et al. 2021

Preprint

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A common challenge in drug design pertains to finding chemical modifications to a ligand that increases its affinity to the target protein. An underutilised advance is the increase in structural biology throughput, which has progressed from an artisanal endeavour to a monthly throughput of up to 100 different ligands against a protein in modern synchrotrons. However, the missing piece is a framework that turns high throughput crystallography data into predictive models for ligand design. Here we designed a simple machine learning approach that predicts protein-ligand affinity from experimental structures of diverse ligands against a single protein paired with biochemical measurements. Our key insight is using physics-based energy descriptors to represent protein-ligand complexes, and a learning-to-rank approach that infers the relevant differences between binding modes. We ran a high throughput crystallography campaign against the SARS-CoV-2 Main Protease (MPro), obtaining parallel measurements of over 200 protein-ligand complexes and the binding activity. This allows us to design a one-step library syntheses which improved the potency of two distinct micromolar hits by over 10-fold, arriving at a non-covalent and non-peptidomimetic inhibitor with 120 nM antiviral efficacy. Crucially, our approach successfully extends ligands to unexplored regions of the binding pocket, executing large and fruitful moves in chemical space with simple chemistry.

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Green Core Competencies, Green Process Innovation, and Firm Performance: The Moderating Role of Sustainability Consciousness, a Mixed Method Study on Golf Hotels

Ozilhan Ozbey,

Coskun Degirmen,

Berk

et al. 2024

Sustainability

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Sustainability of biological, social, and economic systems is crucial for protecting our common future and preserving the balance between nature and humans. Environmental concerns should be adopted by all units of society and sustainability awareness should be adapted to all processes through optimum technologies both in daily life and in business management. The basic objective of this article is to determine the effects of green core competencies, green process innovation, and firm performance variables on each other and to examine the moderating role of sustainability consciousness on these effects. A survey and semi-structured interview forms were preferred as data collection methods. In the analysis of the survey data, AMOS was adopted to test the hypothetical model and the Hayes Process macro was employed to determine the moderating effect. The data of interview forms were analyzed with the bag of words model. The research results show that green core competencies positively affect green process innovation and green process innovation positively affects firm performance. In addition, the moderating effect of the attitudinal and behavioral dimensions of sustainability awareness on the impact of green process innovation on firm performance is supported, while the moderating effect of the sustainability knowingness dimension is not supported.

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Profiling and analysis of chemical compounds using pointwise mutual information

Cited by 3 publications

References 61 publications

New Investigations with Lupane Type A-Ring Azepane Triterpenoids for Antimycobacterial Drug Candidate Design

New Investigations with Lupane Type A-Ring Azepane Triterpenoids for Antimycobacterial Drug Candidate Design

Turning high-throughput structural biology into predictive inhibitor design

Green Core Competencies, Green Process Innovation, and Firm Performance: The Moderating Role of Sustainability Consciousness, a Mixed Method Study on Golf Hotels

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