Energy-based prediction of amino acid-nucleotide base recognition

Anna Marabotti, Francesca Spyrakis, Angelo Facchiano, Pietro Cozzini, Saverio Alberti, Glen E. Kellogg, Andrea Mozzarelli

Research output: Contribution to journalArticlepeer-review


Despite decades of investigations, it is not yet clear whether there are rules dictating the specificity of the interaction between amino acids and nucleotide bases. This issue was addressed by determining, in a dataset consisting of 100 high-resolution protein-DNA structures, the frequency and energy of interaction between each amino acid and base, and the energetics of water-mediated interactions. The analysis was carried out using HINT, a non-Newtonian force field encoding both enthalpic and entropic contributions, and Rank, a geometry-based tool for evaluating hydrogen bond interactions. A frequency- and energy-based preferential interaction of Arg and Lys with G, Asp and Glu with C, and Asn and Gln with A was found. Not only favorable, but also unfavorable contacts were found to be conserved. Water-mediated interactions strongly increase the probability of Thr-A, Lys-A, and Lys-C contacts. The frequency, interaction energy, and water enhancement factors associated with each amino acid-base pair were used to predict the base triplet recognized by the helix motif in 45 zinc fingers, which represents an ideal case study for the analysis of one-to-one amino acid-base pair contacts. The model correctly predicted 70.4% of 135 amino acid-base pairs, and, by weighting the energetic relevance of each amino acid-base pair to the overall recognition energy, it yielded a prediction rate of 89.7%.

Original languageEnglish
Pages (from-to)1955-1969
Number of pages15
JournalJournal of Computational Chemistry
Issue number12
Publication statusPublished - Sep 2008


  • Amino acid-base recognition
  • Energy-based code
  • HINT
  • Protein-DNA
  • Zinc finger

ASJC Scopus subject areas

  • Chemistry(all)
  • Safety, Risk, Reliability and Quality


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