Development and Validation of a DFT-Based Force Field for a Hydrated Homoalanine Polypeptide

by Yuan, Ying; Ma, Zhonghua; Wang, Feng

A new force field has been created for simulating hydrated alanine polypeptides using the adaptive force matching (AFM) method. Only density functional theory calculations using the Perdew-Burke-Ernzerhof exchange-correlation functional and the D3 dispersion correction were used to fit the force field. The new force field, AFM2020, predicts NMR scalar coupling constants for hydrated homopolymeric alanine in better agreements with experimental data than several other models including those fitted directly to such data. For Ala(7), the new force field shows about 15% helical conformations, 20% conformation in the beta basin, and 65% polyproline II. The predicted helical population of short hydrated alanine is higher than previous estimates based on the same experimental data. Gas-phase simulations indicate that the force field developed by AFM solution-phase data is likely to produce a reasonable conformation distribution when hydration water is no longer present, such as the interior of a protein.

Journal
Journal of Physical Chemistry B
Volume
125
Issue
6
Year
2021
Start Page
1568-1581
URL
https://dx.doi.org/10.1021/acs.jpcb.0c11618
ISBN/ISSN
1520-5207; 1520-6106
DOI
10.1021/acs.jpcb.0c11618