Secondary structure of rat and human amylin across force fields
The aggregation of human amylin has been strongly implicated in the progression of Type II diabetes. This 37-residue peptide forms a variety of secondary structures, including random coils, α-helices, and β-hairpins. The balance between these structures depends on the chemical environment, making amylin an ideal candidate to examine inherent biases in force fields. Rat amylin differs from human amylin by only 6 residues; however, it does not form fibrils. Therefore it provides a useful complement to human amylin in studies of the key events along the aggregation pathway. In this work, the free energy of rat and human amylin was determined as a function of α-helix and β-hairpin content for the Gromos96 53a6, OPLS-AA/L, CHARMM22/CMAP, CHARMM22*, Amberff99sb*-ILDN, and Amberff03w force fields using advanced sampling techniques, specifically bias exchange metadynamics. This work represents a first systematic attempt to evaluate the conformations and the corresponding free energy of a large, clinically relevant disordered peptide in solution across force fields. The NMR chemical shifts of rIAPP were calculated for each of the force fields using their respective free energy maps, allowing us to quantitatively assess their predictions. We show that the predicted distribution of secondary structures is sensitive to the choice of force-field:more »
- Univ. of Chicago, Chicago, IL (United States). Inst. for Molecular Engineering.
- National Cheng Kung Univ., Tainan (Taiwan). Dept. of Chemical Engineering.
- Univ. of Chicago, Chicago, IL (United States). Inst. for Molecular Engineering; Argonne National Lab. (ANL), Argonne, IL (United States)
- Univ. of Leeds (United Kingdom)
- Publication Date:
- OSTI Identifier:
- Grant/Contract Number:
- Accepted Manuscript
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Volume: 10; Journal Issue: 7; Journal ID: ISSN 1932-6203
- Public Library of Science
- Research Org:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org:
- Country of Publication:
- United States
- 59 BASIC BIOLOGICAL SCIENCES free energy; biochemical simulations; molecular dynamics; proline; intermolecular forces; protein structure prediction; oligomers; molecular structure
Enter terms in the toolbar above to search the full text of this document for pages containing specific keywords.