Proc. Natl. Acad. Sci. USA. 101
, 7960 (2004)
Geometry and symmetry pre-sculpt the free energy landscape of proteins
T. X. Hoang, A. Trovato, F. Seno, J. R. Banavar, and A. Maritan
We present a simple physical model that demonstrates that the native-state folds of proteins can emerge on the basis of considerations of geometry and symmetry. We show that the inherent anisotropy of a chain molecule, the geometrical and energetic constraints placed by the hydrogen bonds and sterics, and hydrophobicity are sufficient to yield a free-energy landscape with broad minima even for a homopolymer. These minima correspond to marginally compact structures comprising the menu of folds that proteins choose from to house their native states in. Our results provide a general framework for understanding the common characteristics of globular proteins.