Improvement of Protein Structure Modeling Upon Coarse Grained Force Field Augmentation with Multitorsional Potentials...

Continuing our work (Petrusevich, E. F.; Liwo, A. J. Phys. Chem. B 2025, 129, 7119-7133), in which the multitorsional potentials accounting for α-helix formation cooperativity, U_mtor^f, have been implemented in the coarse-grained UNRES force field, we have enhanced UNRES with those accounting for the cooperativity of extended strand formation, U_mtor^e. The parameters have been determined by the maximum-likelihood principle using 190,577 extended turn-bordered protein segments from the Protein Data Bank. UNRES augmented with U_mtor^f and U_mtor^e showed improved performance in ab initio protein structure modeling with a set of 76 benchmark proteins of different secondary structure and topology and sizes from 20 to 126 amino-acid residues. A significant part of this improvement was the increased correctness of the secondary structure of the models upon introducing the multitorsional terms. This result demonstrates the significance of along-chain coupling of local conformational states in protein folding, including secondary and tertiary structure formation.