A population-based evolutionary algorithm for sampling minima in the protein energy surface

Sameh Saleh, Brian Olson, Amarda Shehu

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Obtaining a structural characterization of the biologically active (native) state of a protein is a long standing problem in computational biology. The high dimensionality of the conformational space and ruggedness of the associated energy surface are key challenges to algorithms in search of an ensemble of low-energy decoy conformations relevant for the native state. As the native structure does not often correspond to the global minimum energy, diversity is key. We present a memetic evolutionary algorithm to sample a diverse ensemble of conformations that represent low-energy local minima in the protein energy surface. Conformations in the algorithm are members of an evolving population. The molecular fragment replacement technique is employed to obtain children from parent conformations. A greedy search maps a child conformation to its nearest local minimum. Resulting minima and parent conformations are merged and truncated back to the initial population size based on potential energies. Results show that the additional minimization is key to obtaining a diverse ensemble of decoys, circumvent premature convergence to sub-optimal regions in the conformational space, and approach the native structure with IRMSDs comparable to state-of-the-art decoy sampling methods.

Original languageEnglish (US)
Title of host publicationProceedings - 2012 IEEE International Conference on Bioinformatics and Biomedicine Workshops, BIBMW 2012
Pages64-71
Number of pages8
DOIs
StatePublished - 2012
Externally publishedYes
Event2012 IEEE International Conference on Bioinformatics and Biomedicine Workshops, BIBMW 2012 - Philadelphia, PA, United States
Duration: Oct 4 2012Oct 7 2012

Publication series

NameProceedings - 2012 IEEE International Conference on Bioinformatics and Biomedicine Workshops, BIBMW 2012

Conference

Conference2012 IEEE International Conference on Bioinformatics and Biomedicine Workshops, BIBMW 2012
Country/TerritoryUnited States
CityPhiladelphia, PA
Period10/4/1210/7/12

Keywords

  • evolutionary computation
  • greedy local search
  • local minima
  • molecular fragment replacement
  • near-native conformations
  • protein native state

ASJC Scopus subject areas

  • Biomedical Engineering
  • Health Informatics

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