3 years ago

Significantly Improved Protein Folding Thermodynamics Using a Dispersion-Corrected Water Model and a New Residue-Specific Force Field

Significantly Improved Protein Folding Thermodynamics Using a Dispersion-Corrected Water Model and a New Residue-Specific Force Field
Hao-Nan Wu, Fan Jiang, Yun-Dong Wu
An accurate potential energy model is crucial for biomolecular simulations. Despite many recent improvements of classical protein force fields, there are remaining key issues: much weaker temperature dependence of folding/unfolding equilibrium and overly collapsed unfolded or disordered states. For the latter problem, a new water model (TIP4P-D) has been proposed to correct the significantly underestimated water dispersion interactions. Here, using TIP4P-D, we reveal problems in current force fields through failures in folding model systems (a polyalanine peptide, Trp-cage, and the GB1 hairpin). By using residue-specific parameters to achieve better match between amino acid sequences and native structures and adding a small H-bond correction to partially compensate the missing many-body effects in α-helix formation, the new RSFF2+ force field with the TIP4P-D water model can excellently reproduce experimental melting curves of both α-helical and β-hairpin systems. The RSFF2+/TIP4P-D method also gives less collapsed unfolded structures and describes well folded proteins simultaneously.

Publisher URL: http://dx.doi.org/10.1021/acs.jpclett.7b01213

DOI: 10.1021/acs.jpclett.7b01213

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