Secondary Forces in Protein Folding
Name
nihms-1067149.pdf
Description
Accepted version
Size
2.33 MB
Format
Adobe PDF
Checksum (MD5)
394fa7df06e7d1d994bea91c2e52a4aa
Author(s)
Newberry, Robert W.
Raines, Ronald T
Date Issued
June 2019
Journal
ACS Chemical Biology
Publisher
American Chemical Society (ACS)
Citation
Newberry, Robert W. and Ronald T. Raines. "Secondary Forces in Protein Folding." ACS Chemical Biology 14, 8 (June 2019): 1677–1686 © 2019 American Chemical Society
Version
Author's final manuscript
Abstract
© 2019 American Chemical Society. A complete inventory of the forces governing protein folding is critical for productive protein modeling, including structure prediction and de novo design, as well as understanding protein misfolding diseases of clinical significance. The dominant contributors to protein folding include the hydrophobic effect and conventional hydrogen bonding, along with Coulombic and van der Waals interactions. Over the past few decades, important additional contributors have been identified, including C-H···O hydrogen bonding, n→π∗ interactions, C5 hydrogen bonding, chalcogen bonding, and interactions involving aromatic rings (cation-π, X-H···π, π-π, anion-π, and sulfur-arene). These secondary contributions fall into two general classes: (1) weak but abundant interactions of the protein main chain and (2) strong but less frequent interactions involving protein side chains. Though interactions with high individual energies play important roles in specifying nonlocal molecular contacts and ligand binding, we estimate that weak but abundant interactions are likely to make greater overall contributions to protein folding, particularly at the level of secondary structure. Further research is likely to illuminate additional roles of these noncanonical interactions and could also reveal contributions yet unknown.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/acschembio.9b00339
