Abstract
We determined an empirical correlation that relates the amide I vibrational band frequencies of the glutamine (Q) side chain to the strength of hydrogen bonding, van der Waals, and Lewis acid-base interactions of its primary amide carbonyl. We used this correlation to determine the Q side chain carbonyl interaction enthalpy (ΔHint) in monomeric and amyloid-like fibril conformations of D2Q10K2 (Q10). We independently verified these ΔHint values through molecular dynamics simulations that showed excellent agreement with experiments. We found that side chain-side chain and side chain-peptide backbone interactions in fibrils and monomers are more enthalpically favorable than are Q side chain-water interactions. Q10 fibrils also showed a more favorable ΔHint for side chain-side chain interactions compared to backbone-backbone interactions. This work experimentally demonstrates that interamide side chain interactions are important in the formation and stabilization of polyQ fibrils.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1944-1950 |
| Number of pages | 7 |
| Journal | Journal of Physical Chemistry Letters |
| Volume | 9 |
| Issue number | 8 |
| DOIs | |
| State | Published - Apr 19 2018 |
Bibliographical note
Funding Information:Funding for this work was provided by the University of Pittsburgh (D.P., R.S.J., S.A.A.), the Defense Threat Reduction Agency HDTRA1-09-14-FRCWMD (R.S.J., S.A.A.), and NIH R01 DA027806 (R.J.W.). MD simulation computer time was supported by XSEDE MCB060069, and computer equipment was purchased from NSF funds (CHE-1126465 and P116Z080180). We thank the late Prof. Jeffry Madura (Duquesne University, Department of Chemistry and Biochemistry) for useful discussions. Also, we thank Stephen White (University of Pittsburgh, Molecular Biophysics and Structural Biology Program), Tim Coleman (University of Pittsburgh, Department of Statistics), and Prof. Satish Iyengar (University of Pittsburgh, Department of Statistics) for assistance in our error estimation.
Funding Information:
This work was provided by the University of Pittsburgh (D.P., R.S.J., S.A.A.), the Defense Threat Reduction Agency HDTRA1-09-14-FRCWMD (R.S.J., S.A.A.), and NIH R01 DA027806 (R.J.W.). MD simulation computer time was supported by XSEDE MCB060069 and computer equipment was purchased from NSF funds (CHE-1126465 and P116Z080180). We thank the late Prof. Jeffry Madura (Duquesne University Department of Chemistry and Biochemistry) for useful discussions. Also, we thank Stephen White (University of Pittsburgh, Molecular Biophysics and Structural Biology Program), Tim Coleman (University of Pittsburgh, Department of Statistics), and Prof. Satish Iyengar (University of Pittsburgh, Department of Statistics) for assistance in our error estimation.
Publisher Copyright:
© 2018 American Chemical Society.