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Ligand Shaping in Induced Fit Docking of MraY Inhibitors. Polynomial Discriminant and Laplacian Operator as Biological Activity Descriptors

Docking—i.e., interaction of a small molecule (ligand) with a proteic structure (receptor)—represents the ground of drug action mechanism of the vast majority of bioactive chemicals. Ligand and receptor accommodate their geometry and energy, within this interaction, in the benefit of receptor–ligand...

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Detalles Bibliográficos
Autores principales: Lungu, Claudiu N., Diudea, Mircea V., Putz, Mihai V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535870/
https://www.ncbi.nlm.nih.gov/pubmed/28653980
http://dx.doi.org/10.3390/ijms18071377
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author Lungu, Claudiu N.
Diudea, Mircea V.
Putz, Mihai V.
author_facet Lungu, Claudiu N.
Diudea, Mircea V.
Putz, Mihai V.
author_sort Lungu, Claudiu N.
collection PubMed
description Docking—i.e., interaction of a small molecule (ligand) with a proteic structure (receptor)—represents the ground of drug action mechanism of the vast majority of bioactive chemicals. Ligand and receptor accommodate their geometry and energy, within this interaction, in the benefit of receptor–ligand complex. In an induced fit docking, the structure of ligand is most susceptible to changes in topology and energy, comparative to the receptor. These changes can be described by manifold hypersurfaces, in terms of polynomial discriminant and Laplacian operator. Such topological surfaces were represented for each MraY (phospho-MurNAc-pentapeptide translocase) inhibitor, studied before and after docking with MraY. Binding affinities of all ligands were calculated by this procedure. For each ligand, Laplacian and polynomial discriminant were correlated with the ligand minimum inhibitory concentration (MIC) retrieved from literature. It was observed that MIC is correlated with Laplacian and polynomial discriminant.
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spelling pubmed-55358702017-08-04 Ligand Shaping in Induced Fit Docking of MraY Inhibitors. Polynomial Discriminant and Laplacian Operator as Biological Activity Descriptors Lungu, Claudiu N. Diudea, Mircea V. Putz, Mihai V. Int J Mol Sci Article Docking—i.e., interaction of a small molecule (ligand) with a proteic structure (receptor)—represents the ground of drug action mechanism of the vast majority of bioactive chemicals. Ligand and receptor accommodate their geometry and energy, within this interaction, in the benefit of receptor–ligand complex. In an induced fit docking, the structure of ligand is most susceptible to changes in topology and energy, comparative to the receptor. These changes can be described by manifold hypersurfaces, in terms of polynomial discriminant and Laplacian operator. Such topological surfaces were represented for each MraY (phospho-MurNAc-pentapeptide translocase) inhibitor, studied before and after docking with MraY. Binding affinities of all ligands were calculated by this procedure. For each ligand, Laplacian and polynomial discriminant were correlated with the ligand minimum inhibitory concentration (MIC) retrieved from literature. It was observed that MIC is correlated with Laplacian and polynomial discriminant. MDPI 2017-06-27 /pmc/articles/PMC5535870/ /pubmed/28653980 http://dx.doi.org/10.3390/ijms18071377 Text en © 2017 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lungu, Claudiu N.
Diudea, Mircea V.
Putz, Mihai V.
Ligand Shaping in Induced Fit Docking of MraY Inhibitors. Polynomial Discriminant and Laplacian Operator as Biological Activity Descriptors
title Ligand Shaping in Induced Fit Docking of MraY Inhibitors. Polynomial Discriminant and Laplacian Operator as Biological Activity Descriptors
title_full Ligand Shaping in Induced Fit Docking of MraY Inhibitors. Polynomial Discriminant and Laplacian Operator as Biological Activity Descriptors
title_fullStr Ligand Shaping in Induced Fit Docking of MraY Inhibitors. Polynomial Discriminant and Laplacian Operator as Biological Activity Descriptors
title_full_unstemmed Ligand Shaping in Induced Fit Docking of MraY Inhibitors. Polynomial Discriminant and Laplacian Operator as Biological Activity Descriptors
title_short Ligand Shaping in Induced Fit Docking of MraY Inhibitors. Polynomial Discriminant and Laplacian Operator as Biological Activity Descriptors
title_sort ligand shaping in induced fit docking of mray inhibitors. polynomial discriminant and laplacian operator as biological activity descriptors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535870/
https://www.ncbi.nlm.nih.gov/pubmed/28653980
http://dx.doi.org/10.3390/ijms18071377
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