Strengths of Hydrogen Bonds Involving Phosphorylated Amino Acid Side Chains

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• 作者：Daniel J. Mandell ; Ilya Chorny ; Eli S. Groban ; Sergio E. Wong ; Elisheva Levine ; Chaya S. Rapp ; Matthew P. Jacobson
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：January 31, 2007
• 年：2007
• 卷：129
• 期：4
• 页码：820 - 827
• 全文大小：113K
• 年卷期：v.129,no.4(January 31, 2007)
• ISSN：1520-5126

文摘

Post-translational phosphorylation plays a key role in regulating protein function. Here, we providea quantitative assessment of the relative strengths of hydrogen bonds involving phosphorylated aminoacid side chains (pSer, pAsp) with several common donors (Arg, Lys, and backbone amide groups). Weutilize multiple levels of theory, consisting of explicit solvent molecular dynamics, implicit solvent molecularmechanics, 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, hydrogenbonds 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 tobe 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 phosphateprotonation state on the strengths of the hydrogen bonds is remarkably subtle, with a more pronouncedeffect on pAsp than on pSer.