Computer-based Design of β-sheet Containing Proteins Public Deposited

Downloadable Content

Download PDF
Alternate title
  • Computer-based Design of [beta]-sheet Containing Proteins
Last Modified
  • March 20, 2019
Creator
  • Kim, Doo Nam
    • Affiliation: School of Medicine, Department of Biochemistry and Biophysics
Abstract
  • Protein design is an excellent test of the minimal determinants of protein structure. Although 70% of naturally occurring proteins contain β-sheets, most previous design efforts have been limited to α-helix bundle proteins or the redesign of naturally occurring proteins. Here, we test and develop computer based methods for designing proteins rich in β-strands. The molecular modeling program Rosetta was used for three separate design tasks: (1) the design of α/β and α+β proteins with a new method called SEWING, which builds proteins from pieces of naturally occurring proteins, (2) the stabilization of β-sheet proteins via the redesign of surface-facing residues, and (3) the de novo design of β-sandwich proteins. This research showed that it is possible to extend the SEWING method to non-α-helix proteins, allowing the incorporation of structural features found in nature, and that it is possible to dramatically boost protein thermal stability (> 25oC) with the redesign β-sheet surfaces. However, we also found that the de novo design of β-sandwich proteins still remains an elusive goal.
Date of publication
Keyword
Resource type
Rights statement
  • In Copyright
Advisor
  • Lee, Andrew
  • Kuhlman, Brian
  • Zhang, Qi
  • Erickson, Harold
  • Richardson, Jane
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
Language
Parents:

This work has no parents.

Items