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Published November 15, 2004 | public
Journal Article

Preprocessing of rotamers for protein design calculations


We have developed a process that significantly reduces the number of rotamers in computational protein design calculations. This process, which we call Vegas, results in dramatic computational performance increases when used with algorithms based on the dead-end elimination (DEE) theorem. Vegas estimates the energy of each rotamer at each position by fixing each rotamer in turn and utilizing various search algorithms to optimize the remaining positions. Algorithms used for this context specific optimization can include Monte Carlo, self-consistent mean field, and the evaluation of an expression that generates a lower bound energy for the fixed rotamer. Rotamers with energies above a user-defined cutoff value are eliminated. We found that using Vegas to preprocess rotamers significantly reduced the calculation time of subsequent DEE-based algorithms while retaining the global minimum energy conformation. For a full boundary design of a 51 amino acid fragment of engrailed homeodomain, the total calculation time was reduced by 12-fold.

Additional Information

© 2004 Wiley Periodicals, Inc. Received 23 April 2004; Accepted 12 June 2004. Article first published online: 27 Aug. 2004. Contract/grant sponsor: National Institutes of Health (P.S.S. and G.K.H.). Contract/grant sponsor: Howard Hughes Medical Institute (S.L.M.). Contract/grant sponsor: Ralph M. Parsons Foundation (S.L.M.). Contract/grant sponsor: IBM Shared University Research Grant (S.L.M.). The authors would like to thank Marie Ary for critical review of the manuscript and offering valuable comments.

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