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

Gaurav Sharma, Kaushal Rege, David E. Budil, Martin L. Yarmush, Constantinos Mavroidis

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

We describe the molecular dynamics (MD)-aided engineering design of mutant peptides based on the α-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 Å (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.

Original languageEnglish (US)
Pages (from-to)505-521
Number of pages17
JournalInternational Journal of Nanomedicine
Volume3
Issue number4
StatePublished - 2008

Fingerprint

Computer Simulation
Peptides
DNA
Chemical Phenomena
Leucine Zippers
Transcription factors
Fasteners
Molecular Dynamics Simulation
Static Electricity
Macromolecules
Molecular dynamics
Structural properties
Electrostatics
Transcription Factors
Modulation
Engineers
Equipment and Supplies

Keywords

  • Bionanotechnology
  • Coiled-coil
  • Environmentally responsive peptides
  • GCN4
  • Leucine zipper
  • Molecular dynamics
  • Nanotweezers
  • Transcription factor engineering

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Organic Chemistry
  • Drug Discovery

Cite this

Sharma, G., Rege, K., Budil, D. E., Yarmush, M. L., & Mavroidis, C. (2008). Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study. International Journal of Nanomedicine, 3(4), 505-521.

Reversible pH-controlled DNA-binding peptide nanotweezers : An in-silico study. / Sharma, Gaurav; Rege, Kaushal; Budil, David E.; Yarmush, Martin L.; Mavroidis, Constantinos.

In: International Journal of Nanomedicine, Vol. 3, No. 4, 2008, p. 505-521.

Research output: Contribution to journalArticle

Sharma, G, Rege, K, Budil, DE, Yarmush, ML & Mavroidis, C 2008, 'Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study', International Journal of Nanomedicine, vol. 3, no. 4, pp. 505-521.
Sharma, Gaurav ; Rege, Kaushal ; Budil, David E. ; Yarmush, Martin L. ; Mavroidis, Constantinos. / Reversible pH-controlled DNA-binding peptide nanotweezers : An in-silico study. In: International Journal of Nanomedicine. 2008 ; Vol. 3, No. 4. pp. 505-521.
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