Optimizing energy potentials for success in protein tertiary structure prediction

Ting Lan Chiu, Richard A. Goldstein

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Background: Success in solving the protein structure prediction problem relies on the choice of an accurate potential energy function. For a single protein sequence, it has been shown that the potential energy function can be optimized for predictive success by maximizing the energy gap between the correct structure and the ensemble of random structures relative to the distribution of the energies of these random structures (the Z-score). Different methods have been described for implementing this procedure for an ensemble of database proteins. Here, we demonstrate a new approach. Results: For a single protein sequence, the probability of success (i.e. the probability that the folded state is the lowest energy state) is derived. We then maximize the average probability of success for a set of proteins to obtain the optimal potential energy function. This results in maximum attention being focused on the proteins whose structures are difficult but not impossible to predict. Conclusions: Using a lattice model of proteins, we show that the optimal interaction potentials obtained by our method are both more accurate and more likely to produce successful predictions than those obtained by other averaging procedures.

Original languageEnglish (US)
Pages (from-to)223-228
Number of pages6
JournalFolding and Design
Issue number3
StatePublished - 1998

Bibliographical note

Funding Information:
We would like to thank Kurt Hillig and James Raines for computational assistance, and Sridhar Govindarajan and Michael Thompson for helpful discussions. Financial support was provided by the College of Literature, Science, and the Arts, the Program in Protein Structure and Design, the Horace H. Rackham School of Graduate Studies, NIH Grant LM0577, and NSF equipment grant BIR9512955.


  • Contact potential
  • Fold recognition
  • Lattice proteins
  • Protein folding
  • Z- score


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