Kirkwood-Buff approach rescues overcollapse of a disordered protein in canonical protein force fields

• Verfasst von: Mercadante, Davide [VerfasserIn]
• Verfasst von: Gräter, Frauke [VerfasserIn]
• Titel: Kirkwood-Buff approach rescues overcollapse of a disordered protein in canonical protein force fields
• Verf.angabe: Davide Mercadante, Sigrid Milles, Gustavo Fuertes, Dmitri I. Svergun, Edward A. Lemke, and Frauke Gräter
• E-Jahr: 2015
• Jahr: June 1, 2015
• Umfang: 10 S.
• Fussnoten: Gesehen am 29.05.2020
• Titel Quelle: Enthalten in: The journal of physical chemistry <Washington, DC> / B
• Ort Quelle: Washington, DC : Soc., 1997
• Jahr Quelle: 2015
• Band/Heft Quelle: 119(2015), 25, Seite 7975-7984
• ISSN Quelle: 1520-5207
• DOI: doi:10.1021/acs.jpcb.5b03440
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1699062552

Abstract

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.