Cargando…

Three dimensional model of severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain and molecular design of severe acute respiratory syndrome coronavirus helicase inhibitors

The modeling of the severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain was performed using the protein structure prediction Meta Server and the 3D Jury method for model selection, which resulted in the identification of 1JPR, 1UAA and 1W36 PDB structures as suitable templ...

Descripción completa

Detalles Bibliográficos
Autores principales: Hoffmann, Marcin, Eitner, Krystian, von Grotthuss, Marcin, Rychlewski, Leszek, Banachowicz, Ewa, Grabarkiewicz, Tomasz, Szkoda, Tomasz, Kolinski, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Kluwer Academic Publishers 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088412/
https://www.ncbi.nlm.nih.gov/pubmed/16972168
http://dx.doi.org/10.1007/s10822-006-9057-z
_version_ 1783509536378716160
author Hoffmann, Marcin
Eitner, Krystian
von Grotthuss, Marcin
Rychlewski, Leszek
Banachowicz, Ewa
Grabarkiewicz, Tomasz
Szkoda, Tomasz
Kolinski, Andrzej
author_facet Hoffmann, Marcin
Eitner, Krystian
von Grotthuss, Marcin
Rychlewski, Leszek
Banachowicz, Ewa
Grabarkiewicz, Tomasz
Szkoda, Tomasz
Kolinski, Andrzej
author_sort Hoffmann, Marcin
collection PubMed
description The modeling of the severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain was performed using the protein structure prediction Meta Server and the 3D Jury method for model selection, which resulted in the identification of 1JPR, 1UAA and 1W36 PDB structures as suitable templates for creating a full atom 3D model. This model was further utilized to design small molecules that are expected to block an ATPase catalytic pocket thus inhibit the enzymatic activity. Binding sites for various functional groups were identified in a series of molecular dynamics calculation. Their positions in the catalytic pocket were used as constraints in the Cambridge structural database search for molecules having the pharmacophores that interacted most strongly with the enzyme in a desired position. The subsequent MD simulations followed by calculations of binding energies of the designed molecules were compared to ATP identifying the most successful candidates, for likely inhibitors—molecules possessing two phosphonic acid moieties at distal ends of the molecule.
format Online
Article
Text
id pubmed-7088412
institution National Center for Biotechnology Information
language English
publishDate 2006
publisher Kluwer Academic Publishers
record_format MEDLINE/PubMed
spelling pubmed-70884122020-03-23 Three dimensional model of severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain and molecular design of severe acute respiratory syndrome coronavirus helicase inhibitors Hoffmann, Marcin Eitner, Krystian von Grotthuss, Marcin Rychlewski, Leszek Banachowicz, Ewa Grabarkiewicz, Tomasz Szkoda, Tomasz Kolinski, Andrzej J Comput Aided Mol Des Original Paper The modeling of the severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain was performed using the protein structure prediction Meta Server and the 3D Jury method for model selection, which resulted in the identification of 1JPR, 1UAA and 1W36 PDB structures as suitable templates for creating a full atom 3D model. This model was further utilized to design small molecules that are expected to block an ATPase catalytic pocket thus inhibit the enzymatic activity. Binding sites for various functional groups were identified in a series of molecular dynamics calculation. Their positions in the catalytic pocket were used as constraints in the Cambridge structural database search for molecules having the pharmacophores that interacted most strongly with the enzyme in a desired position. The subsequent MD simulations followed by calculations of binding energies of the designed molecules were compared to ATP identifying the most successful candidates, for likely inhibitors—molecules possessing two phosphonic acid moieties at distal ends of the molecule. Kluwer Academic Publishers 2006-09-14 2006 /pmc/articles/PMC7088412/ /pubmed/16972168 http://dx.doi.org/10.1007/s10822-006-9057-z Text en © Springer Science+Business Media B.V. 2006 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Paper
Hoffmann, Marcin
Eitner, Krystian
von Grotthuss, Marcin
Rychlewski, Leszek
Banachowicz, Ewa
Grabarkiewicz, Tomasz
Szkoda, Tomasz
Kolinski, Andrzej
Three dimensional model of severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain and molecular design of severe acute respiratory syndrome coronavirus helicase inhibitors
title Three dimensional model of severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain and molecular design of severe acute respiratory syndrome coronavirus helicase inhibitors
title_full Three dimensional model of severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain and molecular design of severe acute respiratory syndrome coronavirus helicase inhibitors
title_fullStr Three dimensional model of severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain and molecular design of severe acute respiratory syndrome coronavirus helicase inhibitors
title_full_unstemmed Three dimensional model of severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain and molecular design of severe acute respiratory syndrome coronavirus helicase inhibitors
title_short Three dimensional model of severe acute respiratory syndrome coronavirus helicase ATPase catalytic domain and molecular design of severe acute respiratory syndrome coronavirus helicase inhibitors
title_sort three dimensional model of severe acute respiratory syndrome coronavirus helicase atpase catalytic domain and molecular design of severe acute respiratory syndrome coronavirus helicase inhibitors
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088412/
https://www.ncbi.nlm.nih.gov/pubmed/16972168
http://dx.doi.org/10.1007/s10822-006-9057-z
work_keys_str_mv AT hoffmannmarcin threedimensionalmodelofsevereacuterespiratorysyndromecoronavirushelicaseatpasecatalyticdomainandmoleculardesignofsevereacuterespiratorysyndromecoronavirushelicaseinhibitors
AT eitnerkrystian threedimensionalmodelofsevereacuterespiratorysyndromecoronavirushelicaseatpasecatalyticdomainandmoleculardesignofsevereacuterespiratorysyndromecoronavirushelicaseinhibitors
AT vongrotthussmarcin threedimensionalmodelofsevereacuterespiratorysyndromecoronavirushelicaseatpasecatalyticdomainandmoleculardesignofsevereacuterespiratorysyndromecoronavirushelicaseinhibitors
AT rychlewskileszek threedimensionalmodelofsevereacuterespiratorysyndromecoronavirushelicaseatpasecatalyticdomainandmoleculardesignofsevereacuterespiratorysyndromecoronavirushelicaseinhibitors
AT banachowiczewa threedimensionalmodelofsevereacuterespiratorysyndromecoronavirushelicaseatpasecatalyticdomainandmoleculardesignofsevereacuterespiratorysyndromecoronavirushelicaseinhibitors
AT grabarkiewicztomasz threedimensionalmodelofsevereacuterespiratorysyndromecoronavirushelicaseatpasecatalyticdomainandmoleculardesignofsevereacuterespiratorysyndromecoronavirushelicaseinhibitors
AT szkodatomasz threedimensionalmodelofsevereacuterespiratorysyndromecoronavirushelicaseatpasecatalyticdomainandmoleculardesignofsevereacuterespiratorysyndromecoronavirushelicaseinhibitors
AT kolinskiandrzej threedimensionalmodelofsevereacuterespiratorysyndromecoronavirushelicaseatpasecatalyticdomainandmoleculardesignofsevereacuterespiratorysyndromecoronavirushelicaseinhibitors