Role of the <i>n</i>+1 amino acid residue on the deamidation of asparagine in pentapeptides
Hasan H. Ince
F. Aylin Sungur Konuklar
Ilke Ugur
Ö. Alaz Ozcan
Maryam Sayadi
Michael Feig
Viktorya Aviyente
10.6084/m9.figshare.1494728.v2
https://tandf.figshare.com/articles/journal_contribution/Role_of_the_i_n_i_1_amino_acid_residue_on_the_deamidation_of_asparagine_in_pentapeptides/1494728
<div><p>Deamidation plays an important role in biochemical phenomena such as aging. The role of the <i>n</i> + 1 residue on the deamidation of asparagine (asparagine being the <i>n</i>th residue) in three pentapeptide chains (GGNGG, GGNMG and GGNIG) has been analysed with hybrid computational tools. Potentials of mean force at 300 K were calculated from the MD/replica exchange simulations using weighted histogram analysis (WHAM) in explicit water. The snapshots were clustered taking into account the requirements of the plausible deamidation mechanisms, as such the tautomerisation of the asparagine side chain as initial step has been confirmed, based on the proximity of water to the deamidation site. The ultimate goal being to gain an insight on the peptide backbone N-H acidity, quantum mechanical calculations have been carried out. For this purpose, the distribution of Φ/Ψ, Φ<sub>2</sub>/Ψ and end-to-end distances deduced from the WHAM diagrams have been considered and a total of 110 structures have been sampled. These neutral pentapeptides as well as their corresponding anions have been optimised (B3LYP/6-31++G(d,p)) in implicit water in order to gain an insight on the peptide backbone N-H acidity. In this study, we have shown that the open conformations of the neutrals and the anions, which display a β sheet like structure are well populated and their <i>pK<sub>a</sub></i>s rank in the same order as the deamidating half-lives, that is the peptides that deaminate fastest can more readily access conformations that are more acidic.</p></div>
2015-11-27 11:26:00
insight
110 structures
access conformations
deamidation mechanisms
pKas rank
anion
acid residue
GGNMG
md
1 residue
pentapeptide chains
300 K
nth residue
asparagine side chain
gain
acidity
Histogram Analysis
GGNIG
role
WHAM diagrams
pentapeptides Deamidation
B 3LYP
GGNGG
deamidation site