Journal article
Discrepancies between Conformational Distributions of a Polyalanine Peptide in Solution Obtained from Molecular Dynamics Force Fields and Amide I′ Band Profiles
The journal of physical chemistry. B, v 114(51), pp 17201-17208
30 Dec 2010
PMID: 21138254
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Abstract
Structural preferences in the unfolded state of peptides determined by molecular dynamics still contradict experimental data. A remedy in this regard has been suggested by MD simulations with an optimized Amber force field ff03* ( Best, R.; Hummer, G. J. Phys. Chem. B 2009, 113, 9004−9015 ). The simulations yielded a statistical coil distribution for alanine which is at variance with recent experimental results. To check the validity of this distribution, we investigated the peptide H-A5W-OH, which with the exception of the additional terminal tryptophan is analogous to the peptide used to optimize the force fields ff03*. Electronic circular dichroism, vibrational circular dichroism, and infrared spectroscopy as well as J-coupling constants obtained from NMR experiments were used to derive the peptide’s conformational ensemble. Additionally, Förster resonance energy transfer between the terminal chromophores of the fluorescently labeled peptide analogue H-Dbo-A5W-OH was used to determine its average length, from which the end-to-end distance of the unlabeled peptide was estimated. Qualitatively, the experimental 3 J(HN,Cα), VCD, and ECD indicated a preference of alanine for polyproline II-like conformations. The experimental 3 J(HN,Cα) for A5W closely resembles the constants obtained for A5. In order to quantitatively relate the conformational distribution of A5 obtained with the optimized AMBER ff03* force field to experimental data, the former was used to derive a distribution function which expressed the conformational ensemble as a mixture of polyproline II, β-strand, helical, and turn conformations. This model was found to satisfactorily reproduce all experimental J-coupling constants. We employed the model to calculate the amide I′ profiles of the IR and vibrational circular dichroism spectrum of A5W, as well as the distance between the two terminal peptide carbonyls. This led to an underestimated negative VCD couplet and an overestimated distance between terminal carbonyl groups. In order to more accurately account for the experimental data, we changed the distribution parameters based on results recently obtained for the alanine-based tripeptides. The final model, which satisfactorily reproduced amide I′ profiles, J-coupling constant, and the end-to-end distance of A5W, reinforces alanine’s high structural preference for polyproline II. Our results suggest that distributions obtained from MD simulations suggesting a statistical coil-like distribution for alanine are still based on insufficiently accurate force fields.
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Details
- Title
- Discrepancies between Conformational Distributions of a Polyalanine Peptide in Solution Obtained from Molecular Dynamics Force Fields and Amide I′ Band Profiles
- Creators
- Daniel VerbaroIndrajit GhoshWerner M NauReinhard Schweitzer-Stenner
- Publication Details
- The journal of physical chemistry. B, v 114(51), pp 17201-17208
- Publisher
- American Chemical Society; Washington, DC
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemistry
- Web of Science ID
- WOS:000285560100024
- Scopus ID
- 2-s2.0-79953744391
- Other Identifier
- 991014878243104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biophysics
- Chemistry, Physical