A Novel Multi-objectivisation Approach for Optimising the Protein Inverse Folding Problem

  • Sune S. Nielsen
  • Grégoire Danoy
  • Wiktor Jurkowski
  • Juan Luis Jiménez Laredo
  • Reinhard Schneider
  • El-Ghazali Talbi
  • Pascal Bouvry
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 9028)


In biology, the subject of protein structure prediction is of continued interest, not only to chart the molecular map of the living cell, but also to design proteins of new functions. The Inverse Folding Problem (IFP) is in itself an important research problem, but also at the heart of most rational protein design approaches. In brief, the IFP consists in finding sequences that will fold into a given structure, rather than determining the structure for a given sequence - as in conventional structure prediction. In this work we present a Multi Objective Genetic Algorithm (MOGA) using the diversity-as-objective (DAO) variant of multi-objectivisation, to optimise secondary structure similarity and sequence diversity at the same time, hence pushing the search farther into wide-spread areas of the sequence solution-space. To control the high diversity generated by the DAO approach, we add a novel Quantile Constraint (QC) mechanism to discard an adjustable worst quantile of the population. This DAO-QC approach can efficiently emphasise exploitation rather than exploration to a selectable degree achieving a trade-off producing both better and more diverse sequences than the standard Genetic Algorithm (GA). To validate the final results, a subset of the best sequences was selected for tertiary structure prediction. The super-positioning with the original protein structure demonstrated that meaningful sequences are generated underlining the potential of this work.


Inverse Folding Problem Protein design Genetic Algorithm Multi-objectivisation 



Work funded by the National Research Fund of Luxembourg (FNR) as part of the EVOPERF project at the University of Luxembourg with the AFR contract no. 1356145. Experiments were carried out using the HPC facility of the University of Luxembourg [23]


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Sune S. Nielsen
    • 1
  • Grégoire Danoy
    • 1
  • Wiktor Jurkowski
    • 3
  • Juan Luis Jiménez Laredo
    • 4
  • Reinhard Schneider
    • 2
  • El-Ghazali Talbi
    • 5
  • Pascal Bouvry
    • 1
  1. 1.FSTCUniversity of LuxembourgWalferdangeLuxembourg
  2. 2.LCSBUniversity of LuxembourgWalferdangeLuxembourg
  3. 3.TGAC, Norwich Research ParkNorwichUK
  4. 4.LITISUniversité du HavreLe HavreFrance
  5. 5.INRIA Lille, Nord Europe Research CentreLilleFrance

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