Mathematical structural descriptors and mutagenicity assessment: a study with congeneric and diverse datasets$

SAR and QSAR in Environmental Research
Subhabrata MajumdarG D Grunwald

Abstract

Quantitative bioactivity and toxicity assessment of chemical compounds plays a central role in drug discovery as it saves a substantial amount of resources. To this end, high-performance computing has enabled researchers and practitioners to leverage hundreds, or even thousands, of computed molecular descriptors for the activity prediction of candidate compounds. In this paper, we evaluate the utility of two large groups of chemical descriptors by such predictive modelling, as well as chemical structure discovery, through empirical analysis. We use a suite of commercially available and in-house software to calculate molecular descriptors for two sets of chemical mutagens - a homogeneous set of 95 amines, and a diverse set of 508 chemicals. Using calculated descriptors, we model the mutagenic activity of these compounds using a number of methods from the statistics and machine-learning literature, and use robust principal component analysis to investigate the low-dimensional subspaces that characterize these chemicals. Our results suggest that combining different sets of descriptors is likely to result in a better predictive model - but that depends on the compounds being modelled and the modelling technique being used.

References

Mar 1, 1990·Journal of Computer-aided Molecular Design·J J Stewart
Nov 25, 2003·Journal of Chemical Information and Computer Sciences·Vladimir SvetnikBradley P Feuston
Jun 1, 2005·Journal of Chemical Information and Modeling·Vladimir SvetnikQinghua Song
Oct 29, 2009·Journal of Chemical Information and Modeling·Pavel G PolishchukVictor E Kuz'min
Mar 1, 2004·Environmental Toxicology and Pharmacology·Douglas M HawkinsDenise Mills
Oct 7, 2014·Wiley Interdisciplinary Reviews. Computational Molecular Science·John B O Mitchell
Jan 24, 2015·Journal of Speech, Language, and Hearing Research : JSLHR·Jill GilkersonKeith Topping
Mar 2, 2016·Journal of Health Economics·Joseph A DiMasiRonald W Hansen
Apr 19, 2016·International Journal of Molecular Sciences·Claudiu N LunguIreneusz P Grudziński
Dec 14, 2016·Journal of Chemical Information and Modeling·Robert P SheridanEric M Gifford

❮ Previous
Next ❯

Citations

Jun 23, 2020·Expert Opinion on Drug Metabolism & Toxicology·Romualdo BenigniManuela Pavan
Apr 20, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Teodora ConstantinescuIldiko Lung
Oct 1, 2019·SAR and QSAR in Environmental Research·J Devillers, H Devillers

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
PCA

Software Mentioned

MolConnZ
Molecule Drug Discovery Suite
POLLY
Small
Triplet
TOPOCLUJ
MOPAC
R

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.