Strengths of hydrogen bonds involving phosphorylated amino acid side chains

Daniel J. Mandell, Ilya Chorny, Eli S. Groban, Sergio E. Wong, Elisheva Levine, Chaya S. Rapp, Matthew P. Jacobson

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Post-translational phosphorylation plays a key role in regulating protein function. Here, we provide a quantitative assessment of the relative strengths of hydrogen bonds involving phosphorylated amino acid side chains (pSer, pAsp) with several common donors (Arg, Lys, and backbone amide groups). We utilize multiple levels of theory, consisting of explicit solvent molecular dynamics, implicit solvent molecular mechanics, and quantum mechanics with a self-consistent reaction field treatment of solvent. Because the ∼6 pKa of phosphate suggests that -1 and -2 charged species may coexist at physiological pH, hydrogen bonds involving both protonated and deprotonated phosphates for all donor-acceptor pairs are considered. Multiple bonding geometries for the charged-charged interactions are also considered. Arg is shown to be capable of substantially stronger salt bridges with phosphorylated side chains than Lys. A pSer hydrogen-bond acceptor tends to form more stable interactions than a pAsp acceptor. The effect of phosphate protonation state on the strengths of the hydrogen bonds is remarkably subtle, with a more pronounced effect on pAsp than on pSer.

Original languageEnglish (US)
Pages (from-to)820-827
Number of pages8
JournalJournal of the American Chemical Society
Issue number4
StatePublished - Jan 31 2007
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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