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

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 correlationenergy 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 correlationterms was calibrated with a set of four small proteins with basic folds: tryptophan cage variant (TRPI; alpha), Full Sequence Design (FSD; alpha + beta), villin headpiece (villin; alpha), and a truncated FBP-28 WW-domain variant (2MWD; beta) (the NEWCT-4P force field) and, subsequently, with an enhanced set of 9 proteins composed of TRP1 FSD, villin, 1BDC (alpha), 2118 (alpha), 1QHK (alpha +beta), 2N9L (alpha + beta), 1E01 (beta), and 2LX7 (beta) (the NEWCT-9P force held). The NEWCT-9P force held 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 correlationterms 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. Published under license by AIP Publishing.