Back to Search Start Over

A general method for the derivation of the functional forms of the effective energy terms in coarse-grained energy functions of polymers. III. Determination of scale-consistent backbone-local and correlation potentials in the UNRES force field and force-field calibration and validation

Authors :
Liwo, Adam
Sieradzan, Adam K.
Lipska, Agnieszka G.
Czaplewski, Cezary
Joung, InSuk
Żmudzińska, Wioletta
Hałabis, Anna
Ołdziej, Stanisław
Source :
Journal of Chemical Physics; 4/21/2019, Vol. 150 Issue 15, pN.PAG-N.PAG, 24p, 4 Color Photographs, 6 Diagrams, 2 Charts, 8 Graphs
Publication Year :
2019

Abstract

The general theory of the construction of scale-consistent energy terms in the coarse-grained force fields presented in Paper I of this series has been applied to the revision of the UNRES force field for physics-based simulations of proteins. The potentials of mean force corresponding to backbone-local and backbone-correlation energy terms were calculated from the ab initio energy surfaces of terminally blocked glycine, alanine, and proline, and the respective analytical expressions, derived by using the scale-consistent formalism, were fitted to them. The parameters of all these potentials depend on single-residue types, thus reducing their number and preventing over-fitting. The UNRES force field with the revised backbone-local and backbone-correlation terms was calibrated with a set of four small proteins with basic folds: tryptophan cage variant (TRP1; α), Full Sequence Design (FSD; α + β), villin headpiece (villin; α), and a truncated FBP-28 WW-domain variant (2MWD; β) (the NEWCT-4P force field) and, subsequently, with an enhanced set of 9 proteins composed of TRP1, FSD, villin, 1BDC (α), 2I18 (α), 1QHK (α + β), 2N9L (α + β), 1E0L (β), and 2LX7 (β) (the NEWCT-9P force field). The NEWCT-9P force field performed better than NEWCT-4P in a blind-prediction-like test with a set of 26 proteins not used in calibration and outperformed, in a test with 76 proteins, the most advanced OPT-WTFSA-2 version of UNRES with former backbone-local and backbone-correlation terms that contained more energy terms and more optimizable parameters. The NEWCT-9P force field reproduced the bimodal distribution of backbone-virtual-bond angles in the simulated structures, as observed in experimental protein structures. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219606
Volume :
150
Issue :
15
Database :
Complementary Index
Journal :
Journal of Chemical Physics
Publication Type :
Academic Journal
Accession number :
135979880
Full Text :
https://doi.org/10.1063/1.5093015