Improvement of Protein Structure Modeling Upon Coarse Grained Force Field Augmentation with Multitorsional Potentials Demonstrates the Significance of Along-Chain Coupling of Local Conformational States in Protein Folding

Continuing our work (Petrusevich, E. F.; Liwo, A. <i>J. Phys. Chem. B</i> 2025, 129, 7119-7133), in which the multitorsional potentials accounting for α-helix formation cooperativity, <i>U</i>_<i>mtor</i>^<i>f</i>, have been implemented in the coarse-grained UNRES force field, we have enhanced UNRES with those accounting for the cooperativity of extended strand formation, <i>U</i>_<i>mtor</i>^<i>e</i>. 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 <i>U</i>_<i>mtor</i>^<i>f</i> and <i>U</i>_<i>mtor</i>^<i>e</i> showed improved performance in <i>ab initio</i> 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.