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Generalized dead-end elimination algorithms make large-scale protein side-chain structure prediction tractable: implications for protein design and structural genomics.

Publication ,  Journal Article
Looger, LL; Hellinga, HW
Published in: J Mol Biol
March 16, 2001

The dead-end elimination (DEE) theorems are powerful tools for the combinatorial optimization of protein side-chain placement in protein design and homology modeling. In order to reach their full potential, the theorems must be extended to handle very hard problems. We present a suite of new algorithms within the DEE paradigm that significantly extend its range of convergence and reduce run time. As a demonstration, we show that a total protein design problem of 10(115) combinations, a hydrophobic core design problem of 10(244) combinations, and a side-chain placement problem of 10(1044) combinations are solved in less than two weeks, a day and a half, and an hour of CPU time, respectively. This extends the range of the method by approximately 53, 144 and 851 log-units, respectively, using modest computational resources. Small to average-sized protein domains can now be designed automatically, and side-chain placement calculations can be solved for nearly all sizes of proteins and protein complexes in the growing field of structural genomics.

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Published In

J Mol Biol

DOI

ISSN

0022-2836

Publication Date

March 16, 2001

Volume

307

Issue

1

Start / End Page

429 / 445

Location

Netherlands

Related Subject Headings

  • X-Ray Diffraction
  • Viral Regulatory and Accessory Proteins
  • Viral Proteins
  • Sequence Homology, Amino Acid
  • Repressor Proteins
  • Protein Folding
  • Protein Engineering
  • Protein Conformation
  • Models, Chemical
  • Immunoglobulin Fab Fragments
 
Journal cover image

Published In

J Mol Biol

DOI

ISSN

0022-2836

Publication Date

March 16, 2001

Volume

307

Issue

1

Start / End Page

429 / 445

Location

Netherlands

Related Subject Headings

  • X-Ray Diffraction
  • Viral Regulatory and Accessory Proteins
  • Viral Proteins
  • Sequence Homology, Amino Acid
  • Repressor Proteins
  • Protein Folding
  • Protein Engineering
  • Protein Conformation
  • Models, Chemical
  • Immunoglobulin Fab Fragments