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Computational Design of Self-Assembling Proteins and Protein-DNA Nanowires


Mou, Yun (2014) Computational Design of Self-Assembling Proteins and Protein-DNA Nanowires. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9PG1PPV.


Computational protein design (CPD) is a burgeoning field that uses a physical-chemical or knowledge-based scoring function to create protein variants with new or improved properties. This exciting approach has recently been used to generate proteins with entirely new functions, ones that are not observed in naturally occurring proteins. For example, several enzymes were designed to catalyze reactions that are not in the repertoire of any known natural enzyme. In these designs, novel catalytic activity was built de novo (from scratch) into a previously inert protein scaffold. In addition to de novo enzyme design, the computational design of protein-protein interactions can also be used to create novel functionality, such as neutralization of influenza. Our goal here was to design a protein that can self-assemble with DNA into nanowires. We used computational tools to homodimerize a transcription factor that binds a specific sequence of double-stranded DNA. We arranged the protein-protein and protein-DNA binding sites so that the self-assembly could occur in a linear fashion to generate nanowires. Upon mixing our designed protein homodimer with the double-stranded DNA, the molecules immediately self-assembled into nanowires. This nanowire topology was confirmed using atomic force microscopy. Co-crystal structure showed that the nanowire is assembled via the desired interactions. To the best of our knowledge, this is the first example of a protein-DNA self-assembly that does not rely on covalent interactions. We anticipate that this new material will stimulate further interest in the development of advanced biomaterials.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:computational protein design, de novo design, protein-protein interaction, molecular dynamics, homodimer, protein-DNA interaction, nanomaterial
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Mayo, Stephen L.
Thesis Committee:
  • Barton, Jacqueline K. (chair)
  • Gray, Harry B.
  • Clemons, William M.
  • Mayo, Stephen L.
Defense Date:21 May 2014
Record Number:CaltechTHESIS:05232014-201621983
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8392
Deposited By: Yun Mou
Deposited On:21 Mar 2016 23:25
Last Modified:04 Oct 2019 00:05

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