Source:Journal of Chemical Theory and Computation, 14 (4):2277–2287, 2018
<p>We recently developed a new coarse-grained model of protein structure and dynamics [Dawid et al. J. Chem. Theory Comput. 2017, 13(11), 5766−5779]. The model assumed a single bead representation of amino acid residues, where positions of such united residues were defined by centers of mass of four amino acid fragments. Replica exchange Monte Carlo sampling of the model chains provided good pictures of modeled structures and their dynamics. In its generic form the statistical knowledge-based force field of the model has been dedicated for single-domain globular proteins. Sequence-specific interactions are defined by three-letter secondary structure data. In the present work we demonstrate that different assignments and/or predictions of secondary structures are usually sufficient for enforcing cooperative formation of native-like folds of SURPASS chains for the majority of single-domain globular proteins. Simulations of native-like structure assembly for a representative set of globular proteins have shown that the accuracy of secondary structure data is usually not crucial for model performance, although some specific errors can strongly distort the obtained three-dimensional structures.</p>
The concept of SURPASS representation is very simple and assumes averaging of short secondary structure fragments. The specific interaction model distinguishes the protein-like SURPASS chain from a random polymer. SURPASS model was used for replica exchange Monte Carlo dynamics simulation of single-domain proteins, with secondary structure as the only sequence-dependent input data for the interaction model. Despite its deep simplification, SURPASS model reproduces reasonably well the basic structural properties of proteins. For both small and larger systems, the accuracy of resulting models was quite good for such level of coarse-graining and trajectories contain a fraction of native-like structures.
The role of secondary structure assignment/prediction in the protein folding process was also investigated. A stepwise shortening of secondary structure elements in the SURPASS simulation proved that even fragmentary information was sufficient for quite effective identification of native-like topology. Critical errors in the assignment or prediction of a secondary structure, such as the substitution of several elements of a secondary structure with one or a replacement of the helix with a beta sheet (or vice versa) lead to a deformation of the structure.