Journal article
The pH-Independence of Trialanine and the Effects of Termini Blocking in Short Peptides: A Combined Vibrational, NMR, UVCD, and Molecular Dynamics Study
The journal of physical chemistry. B, v 117(14), pp 3689-3706
11 Apr 2013
PMID: 23448349
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Abstract
Several lines of evidence now well establish that unfolded peptides in general, and alanine in specific, have an intrinsic preference for the polyproline II (pPII) conformation. Investigation of local order in the unfolded state is, however, complicated by experimental limitations and the inherent dynamics of the system, which has in some cases yielded inconsistent results from different types of experiments. One method of studying these systems is the use of short model peptides, and specifically short alanine peptides, known for predominantly sampling pPII structure in aqueous solution. Recently, He et al. (
J. Am. Chem. Soc.
2012, 134, 1571–1576) proposed that unblocked tripeptides may not be suitable models for studying conformational propensities in unfolded peptides due to the presence of end effect, i.e. electrostatic interactions between investigated amino acid residues and terminal charges. To determine whether changing the protonation states of the N- and C-termini influence the conformational manifold of the central amino acid residue in tripeptides, we have examined the pH-dependence of unblocked trialanine and the conformational preferences of alanine in the alanine dipeptide. To this end, we measured and globally analyzed amide I’ band profiles and NMR J-coupling constants. We described conformational distributions as the superposition of two-dimensional Gaussian distributions assignable to specific sub-spaces of the Ramachandran plot. Results show that the conformational ensemble of trialanine as a whole, and the pPII content (χ
pPII
=0.84) in particular, remain practically unaffected by changing the protonation state. We found that compared to trialanine, the alanine dipeptide has slightly lower pPII content (χ
pPII
=0.74) and an ensemble more reminiscent of the unblocked Gly-Ala-Gly model peptide. In addition, a two-state thermodynamic analysis of the conformational sensitive Δε(T) and
3
J(H
N
H
α
)(T) data obtained from electronic circular dichroism and H-NMR spectra indicate that the free energy landscape of trialanine is similar in all protonation states. MD simulations for the investigated peptides corroborate this notion and show further that the hydration shell around unblocked trialanine is unaffected by the protonation/deprotonation of the C-terminal group. In contrast, the alanine dipeptide shows a reduced water density around the central residue as well as a less ordered hydration shell, which decreases the pPII propensity and reduces the lifetime of sampled conformations.
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Details
- Title
- The pH-Independence of Trialanine and the Effects of Termini Blocking in Short Peptides: A Combined Vibrational, NMR, UVCD, and Molecular Dynamics Study
- Creators
- Siobhan Toal - Department of Chemistry, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104Derya Meral - Department of Physics, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104Daniel Verbaro - Department of Chemistry, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104Brigita Urbanc - Department of Physics, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104Reinhard Schweitzer-Stenner - Department of Chemistry, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104
- Publication Details
- The journal of physical chemistry. B, v 117(14), pp 3689-3706
- Publisher
- American Chemical Society; Washington, DC
- Grant note
- P01 AG027818 || AG / National Institute on Aging : NIA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics; Chemistry
- Web of Science ID
- WOS:000317552700001
- Scopus ID
- 2-s2.0-84876210074
- Other Identifier
- 991014878325504721
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InCites Highlights
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- Web of Science research areas
- Biophysics
- Chemistry, Physical