Effects of Lattice Constraints in Coarse-Grained Protein Models: A Wang-Landau Study

Using Wang-Landau sampling [1], we compare and contrast folding behavior in coarse-grained models for Crambin -- a 46 amino acid protein. We investigate Crambin in the context of the hydrophobic polar (HP) lattice model [2] and the semi-flexible H0P lattice model [3] -- an extension to the HP model in which an additional monomer type and an interaction accounting for chain-stiffness are included. We also examine folding behavior in the analogous continuum models, with potentials designed specifically to mimic the lattice models. Through analysis of thermodynamic and structural behavior, we paint a clear picture of the folding process in all cases, and gain an understanding of the effects of certain interactions on the folding process, as well as how lattice constraints impact the folding process. As the complexity of the model interactions increases, the two major transitions observed in nature -- the coil-globule collapse and the folding transition, split into multi-step processes, wherein the level of model coarse-graining has a significant impact on the details of the folding.

[1] F. Wang and D. P. Landau, Phys. Rev. Lett. 86, 2050 (2001)
[2] K. A. Dill, Biochemistry 24, 1501 - 9 (1985)
[3] A. C. K. Farris, G. Shi, T. Wüst, and D. P. Landau, J. Chem. Phys. 149 125101 (2018)