title: Strengths of hydrogen bonds involving phosphorylated amino acid side chains.
abstract: 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 approximately 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.
authors.affiliation: Graduate Program in Biological and Medical Informatics, Department of Pharmaceutical Chemistry, and Graduate Group in Biophysics, University of California, San Francisco, California 94143, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Mandell
authors.forename: Ilya
authors.initials: I
authors.lastname: Chorny
authors.forename: Eli S
authors.initials: ES
authors.lastname: Groban
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Wong
authors.forename: Elisheva
authors.initials: E
authors.lastname: Levine
authors.forename: Chaya S
authors.initials: CS
authors.lastname: Rapp
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Jacobson
mesh_terms: D000577:Amides / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D001224:Aspartic Acid / Q000737:chemistry; D003198:Computer Simulation; D018698:Glutamic Acid / Q000737:chemistry; D006860:Hydrogen Bonding; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012694:Serine / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry
chemical_list: D000577:Amides; D000596:Amino Acids; D001224:Aspartic Acid; D018698:Glutamic Acid; D012965:Sodium Chloride; D012694:Serine