Computational design and experimental verification of a symmetric protein homodimer

Abstract

Computational protein design tools use a bottom-up approach that allows for the testing of hypotheses on the relationships between amino acid sequence, protein structure and stability, and biological function. Here, we exploited two computational methods, protein docking and protein sequence optimization, to create a favorable protein–protein interaction between two identical proteins, resulting in a novel homodimer. A stepwise approach proved useful: scaffold stabilization followed by interface design to achieve homodimerization. Our results suggest that for some proteins, stabilization may be required for the successful design of functionality.

Document Details

Document Type
Pub Defense Publication
Publication Date
Aug 12, 2015
Source ID
10.1073/pnas.1505072112

Entities

People

  • Fang-ciao Hsu
  • Po-Ssu Huang
  • Shing-jong Huang
  • Stephen L. Mayo
  • Yun Mou

Organizations

  • California Institute of Technology
  • Gordon and Betty Moore Foundation
  • National Science and Technology Council
  • Office of the Secretary of Defense

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