Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study
Gaurav Sharma1, Kaushal Rege2,3, David E Budil4, Martin L Yarmush2,5, Constantinos Mavroidis1
1Department 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, USA
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.
Keywords: bionanotechnology, nanotweezers, coiled-coil, GCN4, leucine zipper, molecular dynamics, environmentally responsive peptides, transcription factor engineering
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF]