Evaluation of the scale-consistent UNRES force field in template-free prediction of protein structures in the CASP13 experiment

• Published in: Journal of molecular graphics & modelling Vol. 92; no. C; pp. 154 - 166
• Main Authors: Lubecka, Emilia A., Karczyńska, Agnieszka S., Lipska, Agnieszka G., Sieradzan, Adam K., Ziȩba, Karolina, Sikorska, Celina, Uciechowska, Urszula, Samsonov, Sergey A., Krupa, Paweł, Mozolewska, Magdalena A., Golon, Łukasz, Giełdoń, Artur, Czaplewski, Cezary, Ślusarz, Rafał, Ślusarz, Magdalena, Crivelli, Silvia N., Liwo, Adam
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2019; Elsevier
• Subjects: Free and data-assisted modeling; Multiscale modeling; protein structure prediction; Replica-exchange molecular dynamics; UNRES force field; Replica-exchange molecular dynamics; Free and data-assisted modeling; protein structure prediction; Multiscale modeling; UNRES force field
• ISSN: 1093-3263; 1873-4243
• DOI: 10.1016/j.jmgm.2019.07.013

The recent NEWCT-9P version of the coarse-grained UNRES force field for proteins, with scale-consistent formulas for the local and correlation terms, has been tested in the CASP13 experiment of the blind-prediction of protein structure, in the ab initio, contact-assisted, and data-assisted modes. Significant improvement of the performance has been observed with respect to the CASP11 and CASP12 experiments (by over 10 GDT_TS units for the ab initio mode predictions and by over 15 GDT_TS units for the contact-assisted prediction, respectively), which is a result of introducing scale-consistent terms and improved handling of contact-distance restraints. As in previous CASP exercises, UNRES ranked higher in the free modeling category than in the general category that included template based modeling targets. Use of distance restraints from the predicted contacts, albeit many of them were wrong, resulted in the increase of GDT_TS by over 8 units on average and introducing sparse restraints from small-angle X-ray/neutron scattering and chemical cross-link-mass-spectrometry experiments, and ambiguous restraints from nuclear magnetic resonance experiments has also improved the predictions by 8.6, 9.7, and 10.7 GDT_TS units on average, respectively.
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•UNRES coarse-grained force field exhibited major performance improvement in CASP13.•The reason of the improvement are scale-consistent terms that embed atomic structure.•Using predicted contacts through a bounded restraint function improves model quality.•Sparse/ambiguous experimental data improve models in the order SAXS/SANS < XLMS < NMR.