Cargando…

Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus thermoproteolyticus. Possible Antibacterial Agents

The search for new antibacterial agents that could decrease bacterial resistance is a subject in continuous development. Gram-negative and Gram-positive bacteria possess a group of metalloproteins belonging to the MEROPS peptidase (M4) family, which is the main virulence factor of these bacteria. In...

Descripción completa

Detalles Bibliográficos
Autores principales: Lamazares, Emilio, MacLeod-Carey, Desmond, Miranda, Fernando P., Mena-Ulecia, Karel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828527/
https://www.ncbi.nlm.nih.gov/pubmed/33451037
http://dx.doi.org/10.3390/molecules26020386
_version_ 1783641030809092096
author Lamazares, Emilio
MacLeod-Carey, Desmond
Miranda, Fernando P.
Mena-Ulecia, Karel
author_facet Lamazares, Emilio
MacLeod-Carey, Desmond
Miranda, Fernando P.
Mena-Ulecia, Karel
author_sort Lamazares, Emilio
collection PubMed
description The search for new antibacterial agents that could decrease bacterial resistance is a subject in continuous development. Gram-negative and Gram-positive bacteria possess a group of metalloproteins belonging to the MEROPS peptidase (M4) family, which is the main virulence factor of these bacteria. In this work, we used the previous results of a computational biochemistry protocol of a series of ligands designed in silico using thermolysin as a model for the search of antihypertensive agents. Here, thermolysin from Bacillus thermoproteolyticus, a metalloprotein of the M4 family, was used to determine the most promising candidate as an antibacterial agent. Our results from docking, molecular dynamics simulation, molecular mechanics Poisson–Boltzmann (MM-PBSA) method, ligand efficiency, and ADME-Tox properties (Absorption, Distribution, Metabolism, Excretion, and Toxicity) indicate that the designed ligands were adequately oriented in the thermolysin active site. The Lig783, Lig2177, and Lig3444 compounds showed the best dynamic behavior; however, from the ADME-Tox calculated properties, Lig783 was selected as the unique antibacterial agent candidate amongst the designed ligands.
format Online
Article
Text
id pubmed-7828527
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-78285272021-01-25 Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus thermoproteolyticus. Possible Antibacterial Agents Lamazares, Emilio MacLeod-Carey, Desmond Miranda, Fernando P. Mena-Ulecia, Karel Molecules Article The search for new antibacterial agents that could decrease bacterial resistance is a subject in continuous development. Gram-negative and Gram-positive bacteria possess a group of metalloproteins belonging to the MEROPS peptidase (M4) family, which is the main virulence factor of these bacteria. In this work, we used the previous results of a computational biochemistry protocol of a series of ligands designed in silico using thermolysin as a model for the search of antihypertensive agents. Here, thermolysin from Bacillus thermoproteolyticus, a metalloprotein of the M4 family, was used to determine the most promising candidate as an antibacterial agent. Our results from docking, molecular dynamics simulation, molecular mechanics Poisson–Boltzmann (MM-PBSA) method, ligand efficiency, and ADME-Tox properties (Absorption, Distribution, Metabolism, Excretion, and Toxicity) indicate that the designed ligands were adequately oriented in the thermolysin active site. The Lig783, Lig2177, and Lig3444 compounds showed the best dynamic behavior; however, from the ADME-Tox calculated properties, Lig783 was selected as the unique antibacterial agent candidate amongst the designed ligands. MDPI 2021-01-13 /pmc/articles/PMC7828527/ /pubmed/33451037 http://dx.doi.org/10.3390/molecules26020386 Text en © 2021 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
Lamazares, Emilio
MacLeod-Carey, Desmond
Miranda, Fernando P.
Mena-Ulecia, Karel
Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus thermoproteolyticus. Possible Antibacterial Agents
title Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus thermoproteolyticus. Possible Antibacterial Agents
title_full Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus thermoproteolyticus. Possible Antibacterial Agents
title_fullStr Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus thermoproteolyticus. Possible Antibacterial Agents
title_full_unstemmed Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus thermoproteolyticus. Possible Antibacterial Agents
title_short Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus thermoproteolyticus. Possible Antibacterial Agents
title_sort theoretical evaluation of novel thermolysin inhibitors from bacillus thermoproteolyticus. possible antibacterial agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828527/
https://www.ncbi.nlm.nih.gov/pubmed/33451037
http://dx.doi.org/10.3390/molecules26020386
work_keys_str_mv AT lamazaresemilio theoreticalevaluationofnovelthermolysininhibitorsfrombacillusthermoproteolyticuspossibleantibacterialagents
AT macleodcareydesmond theoreticalevaluationofnovelthermolysininhibitorsfrombacillusthermoproteolyticuspossibleantibacterialagents
AT mirandafernandop theoreticalevaluationofnovelthermolysininhibitorsfrombacillusthermoproteolyticuspossibleantibacterialagents
AT menauleciakarel theoreticalevaluationofnovelthermolysininhibitorsfrombacillusthermoproteolyticuspossibleantibacterialagents