Bulletin of Mathematical Biology

, Volume 55, Issue 6, pp 1183–1198 | Cite as

Finding the lowest free energy conformation of a protein is an NP-hard problem: Proof and implications

  • Ron Unger
  • John Moult


The protein folding problem and the notion of NP-completeness and NP-hardness are discussed. A lattice model is suggested to capture the essece of protein folding. For this model we present a proof that finding the lowest free energy conformation belongs to the class of NP-hard problems. The implications of the proof are discussed and we suggest that the natural folding process cannot be considered as a search for the global free energy minimum. However, we suggest an explanation as to why, for many proteins, the native functional conformation maycoincide with the lowest free energy conformation.


Free Energy Conformational Space Hamiltonian Path Polynomial Solution Folding Process 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Society for Mathematical Biology 1993

Authors and Affiliations

  • Ron Unger
    • 2
  • John Moult
    • 1
  1. 1.Center for Advanced Reserch in biotechnology, Maryland Biotechnology InstituteUniversity of MarylandRockvilleU.S.A.
  2. 2.Institute for Advanced Computer StudiesUniversity of MarylandCollege ParkU.S.A.

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