Kirkwood-Buff approach rescues overcollapse of a disordered protein in canonical protein force fields
Understanding the function of intrinsically disordered proteins is intimately related to our capacity to correctly sample their conformational dynamics. So far, a gap between experimentally and computationally derived ensembles exists, as simulations show overcompacted conformers. Increasing evidenc...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
June 1, 2015
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| In: |
The journal of physical chemistry. B, Biophysics, biomaterials, liquids, and soft matter
Year: 2015, Volume: 119, Issue: 25, Pages: 7975-7984 |
| ISSN: | 1520-5207 |
| DOI: | 10.1021/acs.jpcb.5b03440 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1021/acs.jpcb.5b03440 Verlag: https://doi.org/10.1021/acs.jpcb.5b03440 
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| Author Notes: | Davide Mercadante, Sigrid Milles, Gustavo Fuertes, Dmitri I. Svergun, Edward A. Lemke, and Frauke Gräter |
| Summary: | Understanding the function of intrinsically disordered proteins is intimately related to our capacity to correctly sample their conformational dynamics. So far, a gap between experimentally and computationally derived ensembles exists, as simulations show overcompacted conformers. Increasing evidence suggests that the solvent plays a crucial role in shaping the ensembles of intrinsically disordered proteins and has led to several attempts to modify water parameters and thereby favor protein-water over protein-protein interactions. This study tackles the problem from a different perspective, which is the use of the Kirkwood-Buff theory of solutions to reproduce the correct conformational ensemble of intrinsically disordered proteins (IDPs). A protein force field recently developed on such a basis was found to be highly effective in reproducing ensembles for a fragment from the FG-rich nucleoporin 153, with dimensions matching experimental values obtained from small-angle X-ray scattering and single molecule FRET experiments. Kirkwood-Buff theory presents a complementary and fundamentally different approach to the recently developed four-site TIP4P-D water model, both of which can rescue the overcollapse observed in IDPs with canonical protein force fields. As such, our study provides a new route for tackling the deficiencies of current protein force fields in describing protein solvation. |
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| Item Description: | Gesehen am 29.05.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1520-5207 |
| DOI: | 10.1021/acs.jpcb.5b03440 |