Recapturing Cooperativity of α-Helix Formation and Packing in Coarse-Grained Protein Structure Modeling with...

The multitorsional potential accounting for cooperativity of local interactions proposed in our previous work (Sikorska & Liwo, J. Phys. Chem. B, 2022, 126, 9493-9505; 2023, 127, 425-426) has been introduced into the UNRES coarse-grained force field. The parameters of the potential have been found by means of maximum-likelihood principle using the data of 1,092,517 helical segments of protein structures of the Protein Data Bank. The modified UNRES has been tested with a set of 28 α-helical proteins with size from 20 to 126 amino acid residues and various topologies. With the best parametrization, the first-choice models were significantly improved for 10 proteins (ΔGDT_TS > 5) and deteriorated for 3 proteins (ΔGDT_TS < -5). The improvement resulted from strengthening of the helical sections and improving the geometry of the fragments following helix ends, thus enabling correct packing. Overstrengthening the helical sections was the main reason for model deterioration.