Overcoming the Key Challenges in De Novo Protein Design: Enhancing Computational Efficiency and Incorporating True Backbone Flexibility

  • Christodoulos A. Floudas
  • Ho Ki Fung
  • Dimitrios Morikis
  • Martin S. Taylor
  • Li Zhang
Part of the Applied Optimization book series (APOP, volume 102)


De novo protein design is initiated with a postulated or known flexible threedimensional protein structure and aims at identifying amino acid sequences compatible with such a structure. The problem was first denoted as the “inverse folding problem” [4, 5] since protein design has intimate links to the well-known protein folding problem [6]. While the protein folding problem aims at determining the single structure for a sequence, the de novo protein design problem exhibits a high level of degeneracy; that is, a large number of sequences are always found to share a common fold, although the sequences will vary with respect to properties such as activity and stability.

Key words

De novo protein design true protein backbone flexibility weighted average forcefield bin variables fold specificity stage 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Christodoulos A. Floudas
    • 1
  • Ho Ki Fung
    • 1
  • Dimitrios Morikis
    • 2
  • Martin S. Taylor
    • 3
  • Li Zhang
    • 4
  1. 1.Department of Chemical EngineeringPrinceton UniversityPrinceton
  2. 2.Department of BioengineeringUniversity of CaliforniaRiverside
  3. 3.Johns Hopkins University School of MedicineBaltimore
  4. 4.Department of ChemistryUniversity of CaliforniaRiverside

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