In silico structural and functional analysis of the human cytomegalovirus (HHV5) genome

Jiri Novotny, Isidore Rigoutsos, David Coleman, Thomas Shenk

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40 Scopus citations


The open reading frames of human cytomegalovirus (human herpesvirus-5, HHV5) encode some 213 unique proteins with mostly unknown functions. Using the threading program, ProCeryon, we calculated possible matches between the amino acid sequences of these proteins and the Protein Data Bank library of three-dimensional structures. Thirty-six proteins were fully identified in terms of their structure and, often, function; 65 proteins were recognized as members of narrow structural/functional families (e.g. DNA-binding factors, cytokines, enzymes, signaling particles, cell surface receptors etc.); and 87 proteins were assigned to broad structural classes (e.g. all-β, 3-1ayer-αβα, multidomain, etc.). Genes encoding proteins with similar folds, or containing identical structural traits (extreme sequence length, runs of unstructured (Pro and/or Gly-rich) residues, transmembrane segments, etc.) often formed tandem clusters throughout the genome. In the course of this work, benchmarks on about 20 known folds were used to optimize adjustable parameters of threading calculations, i.e. gap penalty weights used in sequence/structure alignments; new scores obtained as simple combinations of existing scoring functions; and number of threading runs conducive to meaningful results. An introduction of summed, per-residue-normalized scores has been essential for discovery of subdomains (EGF-like, SH2, SH3) in longer protein sequences, such as the eight "open sandwich" cytokine domains, 60-70 amino acids long and having the 31β1α fold with one or two disulfide bridges, present in otherwise unrelated proteins.

Original languageEnglish (US)
Pages (from-to)1151-1166
Number of pages16
JournalJournal of Molecular Biology
Issue number5
StatePublished - Jul 27 2001

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Structural Biology


  • Cytomegalovirus
  • Protein folds
  • Stereochemical code
  • Structural genomics
  • Threading


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