Cargando…

HATS5m as an Example of GETAWAY Molecular Descriptor in Assessing the Similarity/Diversity of the Structural Features of 4-Thiazolidinone

Among the various methods for drug design, the approach using molecular descriptors for quantitative structure–activity relationships (QSAR) bears promise for the prediction of innovative molecular structures with bespoke pharmacological activity. Despite the growing number of successful potential a...

Descripción completa

Detalles Bibliográficos
Autores principales: Zapadka, Mariusz, Dekowski, Przemysław, Kupcewicz, Bogumiła
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223869/
https://www.ncbi.nlm.nih.gov/pubmed/35743020
http://dx.doi.org/10.3390/ijms23126576
_version_ 1784733231796453376
author Zapadka, Mariusz
Dekowski, Przemysław
Kupcewicz, Bogumiła
author_facet Zapadka, Mariusz
Dekowski, Przemysław
Kupcewicz, Bogumiła
author_sort Zapadka, Mariusz
collection PubMed
description Among the various methods for drug design, the approach using molecular descriptors for quantitative structure–activity relationships (QSAR) bears promise for the prediction of innovative molecular structures with bespoke pharmacological activity. Despite the growing number of successful potential applications, the QSAR models often remain hard to interpret. The difficulty arises from the use of advanced chemometric or machine learning methods on the one hand, and the complexity of molecular descriptors on the other hand. Thus, there is a need to interpret molecular descriptors for identifying the features of molecules crucial for desirable activity. For example, the development of structure–activity modeling of different molecule endpoints confirmed the usefulness of H-GETAWAY (H-GEometry, Topology, and Atom-Weights AssemblY) descriptors in molecular sciences. However, compared with other 3D molecular descriptors, H-GETAWAY interpretation is much more complicated. The present study provides insights into the interpretation of the HATS5m descriptor (H-GETAWAY) concerning the molecular structures of the 4-thiazolidinone derivatives with antitrypanosomal activity. According to the published study, an increase in antitrypanosomal activity is associated with both a decrease and an increase in HATS5m (leverage-weighted autocorrelation with lag 5, weighted by atomic masses) values. The substructure-based method explored how the changes in molecular features affect the HATS5m value. Based on this approach, we proposed substituents that translate into low and high HATS5m. The detailed interpretation of H-GETAWAY descriptors requires the consideration of three elements: weighting scheme, leverages, and the Dirac delta function. Particular attention should be paid to the impact of chemical compounds’ size and shape and the leverage values of individual atoms.
format Online
Article
Text
id pubmed-9223869
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-92238692022-06-24 HATS5m as an Example of GETAWAY Molecular Descriptor in Assessing the Similarity/Diversity of the Structural Features of 4-Thiazolidinone Zapadka, Mariusz Dekowski, Przemysław Kupcewicz, Bogumiła Int J Mol Sci Article Among the various methods for drug design, the approach using molecular descriptors for quantitative structure–activity relationships (QSAR) bears promise for the prediction of innovative molecular structures with bespoke pharmacological activity. Despite the growing number of successful potential applications, the QSAR models often remain hard to interpret. The difficulty arises from the use of advanced chemometric or machine learning methods on the one hand, and the complexity of molecular descriptors on the other hand. Thus, there is a need to interpret molecular descriptors for identifying the features of molecules crucial for desirable activity. For example, the development of structure–activity modeling of different molecule endpoints confirmed the usefulness of H-GETAWAY (H-GEometry, Topology, and Atom-Weights AssemblY) descriptors in molecular sciences. However, compared with other 3D molecular descriptors, H-GETAWAY interpretation is much more complicated. The present study provides insights into the interpretation of the HATS5m descriptor (H-GETAWAY) concerning the molecular structures of the 4-thiazolidinone derivatives with antitrypanosomal activity. According to the published study, an increase in antitrypanosomal activity is associated with both a decrease and an increase in HATS5m (leverage-weighted autocorrelation with lag 5, weighted by atomic masses) values. The substructure-based method explored how the changes in molecular features affect the HATS5m value. Based on this approach, we proposed substituents that translate into low and high HATS5m. The detailed interpretation of H-GETAWAY descriptors requires the consideration of three elements: weighting scheme, leverages, and the Dirac delta function. Particular attention should be paid to the impact of chemical compounds’ size and shape and the leverage values of individual atoms. MDPI 2022-06-12 /pmc/articles/PMC9223869/ /pubmed/35743020 http://dx.doi.org/10.3390/ijms23126576 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zapadka, Mariusz
Dekowski, Przemysław
Kupcewicz, Bogumiła
HATS5m as an Example of GETAWAY Molecular Descriptor in Assessing the Similarity/Diversity of the Structural Features of 4-Thiazolidinone
title HATS5m as an Example of GETAWAY Molecular Descriptor in Assessing the Similarity/Diversity of the Structural Features of 4-Thiazolidinone
title_full HATS5m as an Example of GETAWAY Molecular Descriptor in Assessing the Similarity/Diversity of the Structural Features of 4-Thiazolidinone
title_fullStr HATS5m as an Example of GETAWAY Molecular Descriptor in Assessing the Similarity/Diversity of the Structural Features of 4-Thiazolidinone
title_full_unstemmed HATS5m as an Example of GETAWAY Molecular Descriptor in Assessing the Similarity/Diversity of the Structural Features of 4-Thiazolidinone
title_short HATS5m as an Example of GETAWAY Molecular Descriptor in Assessing the Similarity/Diversity of the Structural Features of 4-Thiazolidinone
title_sort hats5m as an example of getaway molecular descriptor in assessing the similarity/diversity of the structural features of 4-thiazolidinone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223869/
https://www.ncbi.nlm.nih.gov/pubmed/35743020
http://dx.doi.org/10.3390/ijms23126576
work_keys_str_mv AT zapadkamariusz hats5masanexampleofgetawaymoleculardescriptorinassessingthesimilaritydiversityofthestructuralfeaturesof4thiazolidinone
AT dekowskiprzemysław hats5masanexampleofgetawaymoleculardescriptorinassessingthesimilaritydiversityofthestructuralfeaturesof4thiazolidinone
AT kupcewiczbogumiła hats5masanexampleofgetawaymoleculardescriptorinassessingthesimilaritydiversityofthestructuralfeaturesof4thiazolidinone