Shape and evolution of thermostable protein structure

Organisms evolved at high temperatures must maintain their proteins' structures in the face of increased thermal disorder. This challenge results in differences in residue utilization and overall structure. Focusing on thermostable/mesostable pairs of homologous structures, we have examined these differences using novel geometric measures: specifically burial depth (distance from the molecular surface to each atom) and travel depth (distance from the convex hull to the molecular surface that avoids the protein interior). These along with common metrics like packing and Wadell Sphericity are used to gain insight into the constraints experienced by thermophiles. Mean travel depth of hyperthermostable proteins is significantly less than that of their mesostable counterparts, indicating smaller, less numerous and less deep pockets. The mean burial depth of hyperthermostable proteins is significantly higher than that of mesostable proteins indicating that they bury more atoms further from the surface. The burial depth can also be tracked on the individual residue level, adding a finer level of detail to the standard exposed surface area analysis. Hyperthermostable proteins for the first time are shown to be more spherical than their mesostable homologues, regardless of when and how they adapted to extreme temperature. Additionally, residue specific burial depth examinations reveal that charged residues stay unburied, most other residues are slightly more buried and Alanine is more significantly buried in hyperthermostable proteins. Proteins 2010; 78:420-433. (C) 2009 Wiley-Liss, Inc.