Computational design of a leucine-rich repeat protein with a predefined geometry

Abstract

Repeat proteins are used in nature to bind to proteins and peptides. The shape of their binding surfaces can vary substantially, even for proteins within the same family. This variability likely arose because they evolved to match the proteins they interact with geometrically. Repeat proteins are often engineered to develop binders specific to new target proteins. It would be highly beneficial to design repeat proteins with predefined geometrical shapes because such a method would enable development of engineered repeat proteins that are shape-optimized to their targets. Here, we demonstrate that repeat proteins with a predefined shape can be designed using a computational design method. The approach is exemplified by the design of a protein that forms a ring structure not seen in nature.

Document Details

Document Type
Pub Defense Publication
Publication Date
Nov 26, 2014
Source ID
10.1073/pnas.1413638111

Entities

People

  • Ingemar AndrĂ©
  • Jonas Martinsson
  • Mikael Akke
  • Sebastian Rämisch
  • Ulrich Weininger

Organizations

  • Crafoord Foundation
  • Lund University
  • Swedish Research Council

Tags

Readers

  • Computational Fluid Dynamics (CFD)
  • Molecular Genetics
  • Systems Analysis and Design