Preprocessing of rotamers for protein design calculations

Journal of Computational Chemistry
Premal S ShahStephen L Mayo

Abstract

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.

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Citations

Jul 5, 2005·Nature Reviews. Genetics·Steven A Benner, A Michael Sismour
Jul 25, 2007·Bioinformatics·Ivelin Georgiev, Bruce R Donald
Jun 17, 2014·Bioinformatics·Yichao ZhouJianyang Zeng
Mar 23, 2010·Current Opinion in Structural Biology·Gregory D Friedland, Tanja Kortemme
Jul 14, 2007·Journal of Molecular Biology·Premal S ShahStephen L Mayo
Apr 7, 2006·Protein Science : a Publication of the Protein Society·Louis A ClarkHerman Van Vlijmen
Feb 9, 2005·Biopolymers·Jennifer R CalhounWilliam F DeGrado
May 2, 2007·Journal of Computational Chemistry·Edda KloppmannTorsten Becker
Nov 4, 2009·Journal of Computational Chemistry·Maria Safi, Ryan H Lilien

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