Unevolved de novo proteins have innate tendencies to bind transition metals

Michael S. Wang, Kenric J. Hoegler, Michael H. Hecht

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Life as we know it would not exist without the ability of protein sequences to bind metal ions. Transition metals, in particular, play essential roles in a wide range of structural and catalytic functions. The ubiquitous occurrence of metalloproteins in all organisms leads one to ask whether metal binding is an evolved trait that occurred only rarely in ancestral sequences, or alternatively, whether it is an innate property of amino acid sequences, occurring frequently in unevolved sequence space. To address this question, we studied 52 proteins from a combinatorial library of novel sequences designed to fold into 4-helix bundles. Although these sequences were neither designed nor evolved to bind metals, the majority of them have innate tendencies to bind the transition metals copper, cobalt, and zinc with high nanomolar to low-micromolar affinity.

Original languageEnglish (US)
Article number8
Issue number1
StatePublished - Mar 1 2019

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Palaeontology
  • Space and Planetary Science


  • Binary patterned amino acid sequences
  • Novel metalloproteins
  • Prebiotic chemistry
  • Protein design


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