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The Inverse Protein Folding Problem: Protein Design and Structure Prediction in the Genomic Era

  • Marcel Schmidt am Busch
  • Anne Lopes
  • David Mignon
  • Thomas Gaillard
  • Thomas Simonson

Abstract

Millions of proteins are being identified every year by high throughput genome sequencing projects. Many others can potentially be created by protein engineering and design methods. Here, we review a method for computational protein design (CPD), which starts from a known protein and its 3D structure, and seeks to modify it by mutating some or all of the amino acid sidechains. The mutations are selected to provide stability, and possibly other properties, such as ligand binding. For each set of candidate mutations, the 3D structure is modeled, with an assumption of small, localized perturbations; in particular, we assume the backbone conformation does not change significantly. As in other CPD implementations, the structure is modeled using a classical, molecular mechanics approach along with a simple, implicit description of solvent. Some of the calculations have been distributed to volunteers on the Internet, through our Proteins@Home volunteer computing project. The method and selected results are described, which show that the designed sequences share important properties of natural proteins.

Keywords

Structure Prediction Amino Acid Type Empirical Correction Compute Sequence Rotamer Library 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

We thank the many volunteers who have participated in the Proteins@Home project and contributed computer cycles to this work. See biology.polytechnique.fr/proteinsathome for a complete list of participants. We thank the BOINC development community for testing the alpha version of Proteins@Home.

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Marcel Schmidt am Busch
    • 1
    • 2
  • Anne Lopes
    • 1
  • David Mignon
    • 1
  • Thomas Gaillard
    • 1
  • Thomas Simonson
    • 1
  1. 1.Laboratoire de Biochimie (UMR CNRS 7654), Department of BiologyEcole PolytechniquePalaiseauFrance
  2. 2.Institut fuer theoretische PhysikJohannes Kepler Universitaet LinzLinzAustria

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