Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study

Gaurav Sharma1, Kaushal Rege2,3, David E Budil4, Martin L Yarmush2,5, Constantinos Mavroidis11Department of Mechanical and Industrial Engineering; 4Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA; 2The Center for Engineering in Medicine (CEM), Massachusetts Gen...

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Autores principales:	Gaurav Sharma, Kaushal Rege, David E Budil, Martin L Yarmush, Constantinos Mavroidis
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2008
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/51a2f73c9f664373a6f998ee5b7a00bd
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spelling	oai:doaj.org-article:51a2f73c9f664373a6f998ee5b7a00bd2021-12-02T04:58:03ZReversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study1176-91141178-2013https://doaj.org/article/51a2f73c9f664373a6f998ee5b7a00bd2008-11-01T00:00:00Zhttp://www.dovepress.com/reversible-ph-controlled-dna-binding-peptide-nanotweezers-an-in-silico-a2605https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Gaurav Sharma1, Kaushal Rege2,3, David E Budil4, Martin L Yarmush2,5, Constantinos Mavroidis11Department of Mechanical and Industrial Engineering; 4Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA; 2The Center for Engineering in Medicine (CEM), Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; 3Department of Chemical Engineering, Arizona State University, Tempe, AZ, USA; 5Department of Biomedical Engineering, Rutgers University, NJ, USAAbstract: We describe the molecular dynamics (MD)-aided engineering design of mutant peptides based on the &alpha;-helical coiled-coil GCN4 leucine zipper peptide (GCN4-p1) in order to obtain environmentally-responsive nanotweezers. The actuation mechanism of the nanotweezers depends on the modification of electrostatic charges on the residues along the length of the coiled coil. Modulating the solution pH between neutral and acidic values results in the reversible movement of helices toward and away from each other and creates a complete closed-open-closed transition cycle between the helices. Our results indicate that the mutants show a reversible opening of up to 15 &Aring; (1.5 nm; approximately 150% of the initial separation) upon pH actuation. Investigation on the physicochemical phenomena that influence conformational properties, structural stability, and reversibility of the coiled-coil peptide-based nanotweezers revealed that a rationale- and design-based approach is needed to engineer stable peptide or macromolecules into stimuli-responsive devices. The efficacy of the mutant that demonstrated the most significant reversible actuation for environmentally responsive modulation of DNA-binding activity was also demonstrated. Our results have significant implications in bioseparations and in the engineering of novel transcription factors.Keywords: bionanotechnology, nanotweezers, coiled-coil, GCN4, leucine zipper, molecular dynamics, environmentally responsive peptides, transcription factor engineering Gaurav SharmaKaushal RegeDavid E BudilMartin L YarmushConstantinos MavroidisDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2008, Iss Issue 4, Pp 505-521 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Gaurav Sharma Kaushal Rege David E Budil Martin L Yarmush Constantinos Mavroidis Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study
description	Gaurav Sharma1, Kaushal Rege2,3, David E Budil4, Martin L Yarmush2,5, Constantinos Mavroidis11Department of Mechanical and Industrial Engineering; 4Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA; 2The Center for Engineering in Medicine (CEM), Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; 3Department of Chemical Engineering, Arizona State University, Tempe, AZ, USA; 5Department of Biomedical Engineering, Rutgers University, NJ, USAAbstract: We describe the molecular dynamics (MD)-aided engineering design of mutant peptides based on the &alpha;-helical coiled-coil GCN4 leucine zipper peptide (GCN4-p1) in order to obtain environmentally-responsive nanotweezers. The actuation mechanism of the nanotweezers depends on the modification of electrostatic charges on the residues along the length of the coiled coil. Modulating the solution pH between neutral and acidic values results in the reversible movement of helices toward and away from each other and creates a complete closed-open-closed transition cycle between the helices. Our results indicate that the mutants show a reversible opening of up to 15 &Aring; (1.5 nm; approximately 150% of the initial separation) upon pH actuation. Investigation on the physicochemical phenomena that influence conformational properties, structural stability, and reversibility of the coiled-coil peptide-based nanotweezers revealed that a rationale- and design-based approach is needed to engineer stable peptide or macromolecules into stimuli-responsive devices. The efficacy of the mutant that demonstrated the most significant reversible actuation for environmentally responsive modulation of DNA-binding activity was also demonstrated. Our results have significant implications in bioseparations and in the engineering of novel transcription factors.Keywords: bionanotechnology, nanotweezers, coiled-coil, GCN4, leucine zipper, molecular dynamics, environmentally responsive peptides, transcription factor engineering
format	article
author	Gaurav Sharma Kaushal Rege David E Budil Martin L Yarmush Constantinos Mavroidis
author_facet	Gaurav Sharma Kaushal Rege David E Budil Martin L Yarmush Constantinos Mavroidis
author_sort	Gaurav Sharma
title	Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study
title_short	Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study
title_full	Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study
title_fullStr	Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study
title_full_unstemmed	Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study
title_sort	reversible ph-controlled dna-binding peptide nanotweezers: an in-silico study
publisher	Dove Medical Press
publishDate	2008
url	https://doaj.org/article/51a2f73c9f664373a6f998ee5b7a00bd
work_keys_str_mv	AT gauravsharma reversiblephcontrolleddnabindingpeptidenanotweezersaninsilicostudy AT kaushalrege reversiblephcontrolleddnabindingpeptidenanotweezersaninsilicostudy AT davidebudil reversiblephcontrolleddnabindingpeptidenanotweezersaninsilicostudy AT martinlyarmush reversiblephcontrolleddnabindingpeptidenanotweezersaninsilicostudy AT constantinosmavroidis reversiblephcontrolleddnabindingpeptidenanotweezersaninsilicostudy
_version_	1718400947290374144

Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study

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