Journal
JOURNAL OF COMPUTATIONAL CHEMISTRY
Volume 33, Issue 3, Pages 239-246Publisher
WILEY-BLACKWELL
DOI: 10.1002/jcc.21956
Keywords
acetyl lysine; KQ mutant; Ku; molecular dynamics simulation; docking simulation
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Funding
- Budget for Nuclear Research of the Ministry of Education, Culture, Sports, Science and Technology
- Grants-in-Aid for Scientific Research [22310038, 21510063] Funding Source: KAKEN
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Acetylation of lysine residues, one of the most common protein post-transcriptional modifications, is thought to regulate protein affinity with other proteins or nucleotides. Experimentally, the effects of acetylation have been studied using recombinant mutants in which lysine residues (K) are substituted with glutamine (Q) as a mimic of acetyl lysine (KQ mutant), or with arginine (R) as a mimic of nonacetylated lysine (KR mutant). These substitutions, however, have not been properly validated. The effects lysine acetylation on Ku, a multifunctional protein that has been primarily implicated in DNA repair and cell survival, are characterized herein using a series of computer simulations. The binding free energy was reduced in the KQ mutant, while the KR mutant had no effect, which is consistent with previous experimental results. Unexpectedly, the binding energy between Ku and DNA was maintained at almost the same level as in the wild type protein despite full acetylation of the lysine residues. These results suggest that the effects of acetylation may be overestimated when the KQ mutant is used as a mimic of the acetylated protein. (C) 2011 Wiley Periodicals, Inc. J Comput Chem 2012
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