Size and Shape of Crowders Affect the Folding Landscape of Cytochrome C

Abstract

We use computer simulation to investigate the effects of synthetic crowders on cytochrome c, a small single-domain protein with a cofactor heme. The folding energy landscape of cytochrome was computed in the presence of crowders with various sizes and shapes by using a coarse-grained protein model and the structure-based (Go-like) interactions. Our results demonstrated that given the same volume fraction of crowders, the stability of a folded protein inversely increases with the radius of crowders. In addition, a crowder with an anisotropic geometry imposes a greater stabilizing effect on the folded protein than isotropic crowders. This is in agreement with the predictions by the scaled particle theory. In addition, the distribution of contact formation between heme and cytochrome c protein was found to be varied by different types of crowders, demonstrating that the geometry of crowders may be one of the key factors for tuning heme-protein contact formation under cell-like conditions. Prospects of mixed crowders will be presented.