Abstract
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.
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Unger, R., Moult, J. Finding the lowest free energy conformation of a protein is an NP-hard problem: Proof and implications. Bltn Mathcal Biology 55, 1183–1198 (1993). https://doi.org/10.1007/BF02460703
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DOI: https://doi.org/10.1007/BF02460703