Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities

Detalhes bibliográficos
Autor(a) principal: Polêto, Marcelo D.
Data de Publicação: 2018
Outros Autores: Rusu, Victor H., Grisci, Bruno I., Dorn, Marcio, Lins, Roberto D., Verli, Hugo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/37054
Resumo: Universidade Federal do Rio Grande do Sul. Centro de Biotecnologia. Grupo de Bioinformática Estrutural. Porto Alegre, RS, Brasil.
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spelling Polêto, Marcelo D.Rusu, Victor H.Grisci, Bruno I.Dorn, MarcioLins, Roberto D.Verli, Hugo2019-11-14T13:01:07Z2019-11-14T13:01:07Z2018POLÊTO, Marcelo D. et al. Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities. Frontiers in Pharmacology, v. 9, p. 1-20, 2018.1663-9812https://www.arca.fiocruz.br/handle/icict/3705410.3389/fphar.2018.00395engAromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entitiesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio Grande do Sul. Centro de Biotecnologia. Grupo de Bioinformática Estrutural. Porto Alegre, RS, Brasil.Swiss National Supercomputing Centre. Lugano, Switzerland.Universidade Federal do Rio Grande do Sul. Instituto de Informática. Porto Alegre, RS, Brasil.Universidade Federal do Rio Grande do Sul. Instituto de Informática. Porto Alegre, RS, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Universidade Federal do Rio Grande do Sul. Centro de Biotecnologia. Grupo de Bioinformática Estrutural. Porto Alegre, RS, Brasil.The identification of lead compounds usually includes a step of chemical diversity generation. Its rationale may be supported by both qualitative (SAR) and quantitative (QSAR) approaches, offering models of the putative ligand-receptor interactions. In both scenarios, our understanding of which interactions functional groups can perform is mostly based on their chemical nature (such as electronegativity, volume, melting point, lipophilicity etc.) instead of their dynamics in aqueous, biological solutions (solvent accessibility, lifetime of hydrogen bonds, solvent structure etc.). As a consequence, it is challenging to predict from 2D structures which functional groups will be able to perform interactions with the target receptor, at which intensity and relative abundance in the biological environment, all of which will contribute to ligand potency and intrinsic activity. With this in mind, the aim of this work is to assess properties of aromatic rings, commonly used for drug design, in aqueous solution through molecular dynamics simulations in order to characterize their chemical features and infer their impact in complexation dynamics. For this, common aromatic and heteroaromatic rings were selected and received new atomic charge set based on the direction and module of the dipole moment from MP2/6-31G* calculations, while other topological terms were taken from GROMOS53A6 force field. Afterwards, liquid physicochemical properties were simulated for a calibration set composed by nearly 40 molecules and compared to their respective experimental data, in order to validate each topology. Based on the reliance of the employed strategy, we expanded the dataset to more than 100 aromatic rings. Properties in aqueous solution such as solvent accessible surface area, H-bonds availability, H-bonds residence time, and water structure around heteroatoms were calculated for each ring, creating a database of potential interactions, shedding light on features of drugs in biological solutions, on the structural basis for bioisosterism and on the enthalpic/entropic costs for ligand-receptor complexation dynamics.GromosAromatic ringsDrug designFunctional groupsInteractionsDesenho de Drogasinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83085https://www.arca.fiocruz.br/bitstream/icict/37054/1/license.txt4194663c61da82c21746deb8d6361188MD51ORIGINALAromatic Rings Commonly Used in Medicinal Chemistry_ Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities.pdfAromatic Rings Commonly Used in Medicinal 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dc.title.pt_BR.fl_str_mv Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities
title Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities
spellingShingle Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities
Polêto, Marcelo D.
Gromos
Aromatic rings
Drug design
Functional groups
Interactions
Desenho de Drogas
title_short Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities
title_full Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities
title_fullStr Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities
title_full_unstemmed Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities
title_sort Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities
author Polêto, Marcelo D.
author_facet Polêto, Marcelo D.
Rusu, Victor H.
Grisci, Bruno I.
Dorn, Marcio
Lins, Roberto D.
Verli, Hugo
author_role author
author2 Rusu, Victor H.
Grisci, Bruno I.
Dorn, Marcio
Lins, Roberto D.
Verli, Hugo
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Polêto, Marcelo D.
Rusu, Victor H.
Grisci, Bruno I.
Dorn, Marcio
Lins, Roberto D.
Verli, Hugo
dc.subject.en.pt_BR.fl_str_mv Gromos
Aromatic rings
Drug design
Functional groups
Interactions
topic Gromos
Aromatic rings
Drug design
Functional groups
Interactions
Desenho de Drogas
dc.subject.decs.pt_BR.fl_str_mv Desenho de Drogas
description Universidade Federal do Rio Grande do Sul. Centro de Biotecnologia. Grupo de Bioinformática Estrutural. Porto Alegre, RS, Brasil.
publishDate 2018
dc.date.issued.fl_str_mv 2018
dc.date.accessioned.fl_str_mv 2019-11-14T13:01:07Z
dc.date.available.fl_str_mv 2019-11-14T13:01:07Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv POLÊTO, Marcelo D. et al. Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities. Frontiers in Pharmacology, v. 9, p. 1-20, 2018.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/37054
dc.identifier.issn.pt_BR.fl_str_mv 1663-9812
dc.identifier.doi.none.fl_str_mv 10.3389/fphar.2018.00395
identifier_str_mv POLÊTO, Marcelo D. et al. Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities. Frontiers in Pharmacology, v. 9, p. 1-20, 2018.
1663-9812
10.3389/fphar.2018.00395
url https://www.arca.fiocruz.br/handle/icict/37054
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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